Interleukin-18(IL-18) is a cytokine with many functions. This study was to investigate the serum levels of IL-18 and their clinical significance in patients with colore3ctaql carcinomas. Methods: Peripheral blood samp...Interleukin-18(IL-18) is a cytokine with many functions. This study was to investigate the serum levels of IL-18 and their clinical significance in patients with colore3ctaql carcinomas. Methods: Peripheral blood samples were obtained from 106 patients with colorectal carcinoma and 60 volunteers. The serum IL-18 levels were determined in each sample with an enzyme-linked immunosorbent assay (ELISA). Results: In patients before 1997, the mean IL-18 level was 338.46 pg/ml; in patients after 1997, the mean IL-18 level was 328.85 pg/ml, there is no evidence of loss of IL-18 immunoreactivity after prolonged storage at -80℃. The mean serum IL-18 level in 106 patients with colorectal carcinoma was significantly higher compared with the 60 healthy volunteers (P<0.05). Although the IL-18 level in patients with stage I did not differ from controls, the serum IL-18 levels of patients with stage II, stage III and stage IV disease were significantly higher compared with healthy control (P<0.05). The mean serum IL-18 level of patients with stage III disease, while the difference between patients with stage II and stage IV was not statistically significant (P>0.05). The survival rate of patients with IL-18 levels ≥346 pg/ml (n=47 patients) was significantly worse compared with patients who had IL-18 levels <346 pg/ml(n=57 patients). The 5-year-survival rates were 5.3% and 18.6%, respectively. Multivariate analysis using a Cox proportional hazards model identified the serum IL-18 level as an independent prognostic factor for survival Conclusion: The serum IL-18 level has a significant correlation with survival curve. The serum IL-18 level may represent a significant postoperative prognostic determinant in patients with colorectal carcinoma.展开更多
Recent epidemiological and genetic studies have revealed an interconnection between schizophrenia and breast cancer.The mutual underlying pathophysiological mechanisms may be immunologically driven.A new cluster of mo...Recent epidemiological and genetic studies have revealed an interconnection between schizophrenia and breast cancer.The mutual underlying pathophysiological mechanisms may be immunologically driven.A new cluster of molecules called alarmins may be involved in sterile brain inflammation,and we have already reported the potential impact of interleukin-33(IL-33)on positive symptoms onset and the role of its soluble trans-membranes full length receptor(sST2)on amelioration of negative symptoms in schizophrenia genesis.Furthermore,these molecules have already been shown to be involved in breast cancer etiopathogenesis.In this review article,we aim to describe the IL-33/suppressor of tumorigenicity 2(ST2)axis as a crossroad in schizophreniabreast cancer comorbidity.Considering that raloxifene could be tissue-specific and improve cognition and that tamoxifen resistance in breast carcinoma could be improved by strategies targeting IL-33,these selective estrogen receptor modulators could be useful in complementary treatment.These observations could guide further somatic,as well as psychiatric therapeutical protocols by incorporating what is known about immunity in schizophrenia.展开更多
BACKGROUND As prevalence of nonalcoholic fatty liver disease increases in the population,livers with steatosis will continue to infiltrate the donor pool.Safe utilization of these extended criteria grafts is paramount...BACKGROUND As prevalence of nonalcoholic fatty liver disease increases in the population,livers with steatosis will continue to infiltrate the donor pool.Safe utilization of these extended criteria grafts is paramount given the increased risk associated with their use in transplantation.Prognostic factors that can predict liver dysfunction immediately after transplantation with macrosteatotic grafts are lacking.AIM To understand the relationship between interleukin-33(IL-33)and complement in recipients immediately following liver reperfusion as a marker of liver dysfunction.METHODS Cohort consisted of patients who received a liver transplant from September 2016–September 2019 at our institution.Clinical variables were retrospectively extracted from the electronic medical record.Back-table donor biopsies were obtained with donor steatosis percentage retrospectively determined by a boardcertified pathologist.Blood samples were available immediately following liver transplantation.Quantification of plasma IL-33 and complement proteins,C3a and C5a,were determined by enzyme-linked immunosorbent assay.For mRNA expression,RNA was extracted from donor biopsies and used against a 780 gene panel.RESULTS Cohort consisted of 99 donor and recipients.Donor median age was 45 years and 55%male.Recipients had a median age of 59 years with 62%male.The main etiologies were alcoholic hepatitis,nonalcoholic steatohepatitis,and hepatocellular carcinoma.Median MELD-Na at transplant was 21.Donors were grouped based on moderate macrosteatosis(≥30%).Recipients implanted with moderate macrosteatotic grafts had significantly higher peak alanine aminotransferase/aspartate aminotransferase(P<0.001 and P<0.004),and increased incidence of early allograft dysfunction(60%compared to 18%).Circulating IL-33 levels were significantly elevated in recipients of≥30%macrosteatotic grafts(P<0.05).Recipients with detectable levels of circulating IL-33 immediately following reperfusion had significantly higher alanine aminotransferase/aspartate aminotransferase(P<0.05 and P<0.01).Activated complement(C3a and C5a)were elevated in recipients implanted with moderate macrosteatotic grafts.RNA expression analysis of donor biopsies revealed moderate steatotic grafts upregulated genes inflammatory processes while downregulated hepatocyte-produced complement factors.CONCLUSION Circulating IL-33 and activated complement levels immediately following liver reperfusion in recipients of moderate macrosteatotic grafts may identify which patients are at risk of early allograft dysfunction.展开更多
Interleukin (IL) 33 is a key cytokine in type II immune and airway diseases. It is abundantly expressed in lung epithelial cells and plays an important role in both innate and adaptive immunity. In innate immunity, IL...Interleukin (IL) 33 is a key cytokine in type II immune and airway diseases. It is abundantly expressed in lung epithelial cells and plays an important role in both innate and adaptive immunity. In innate immunity, IL-33 responds promptly to produce an immune response that maintains homeostasis. In adaptive immunity, IL-33 interacts with various immune cells. At the same time, IL-33 also plays an important role in chronic inflammation of the airway and its remodeling. This article reviews the relevant biological knowledge of IL-33 and its research progress in lung immunity, and discusses the related issues of IL-33 as a lung immune test site and therapeutic target.展开更多
Background Acute myocardial infarction (AMI) is a common cardiac emergency with high mortality.Serum soluble ST2 (sST2) is a new emerging biomarker of cardiac diseases.The present study is to investigate the predi...Background Acute myocardial infarction (AMI) is a common cardiac emergency with high mortality.Serum soluble ST2 (sST2) is a new emerging biomarker of cardiac diseases.The present study is to investigate the predictive value of sST2 and interleukin-33 (IL-33) for risk stratification and prognosis in patients with AMI.Methods Fifty-nine patients with AMI,whose chief complaint was chest pain or dyspnea,were selected for our study.Physical examination,chest radiograph,electrocardiograph (ECG),biomarkers of myocardial infarction,NT-proBNP,echocardiography and other relevant examinations were performed to confirm the diagnosis of AMI.Thirty-six healthy people were chosen as the control group.Serum samples from these subjects (patients within 24 hours after acute attack) were collected and the levels of sST2 and IL-33 were assayed by enzyme-linked immuno-sorbent assay (ELISA) kit.The follow-up was performed on the 7th day,28th day,3rd month and 6th month after acute attack.According to the follow-up results we defined the end of observation as recurrence of AMI or any causes of death.Results Median sST2 level of the control group was 9.38ng/ml and that of AMI patients was 29.06ng/ml.Compared with the control group,sST2 expression in the AMI group was significantly different (P〈0.001).In contrast,the IL-33 level showed no significant difference between the two groups.Serum sST2 was a predictive factor independent of other variables and may provide complementary information to NT-proBNP or GRACE risk score.IL-33 had no relationship to recurrence of AMI.Both sST2 and the IL-33/sST2 ratio were correlated with the 6-month prognosis; areas under the ROC curve were 0.938 and 0.920 respectively.Conclusions Early in the course (〈24 hours) of AMI,sST2 usually increases markedly.The increase of sST2 has an independent predictive value for the prognosis in AMI patients and provides complementary information to NT-proBNP or GRACE risk score.The IL-33/sST2 ratio correlates with the 6-month prognosis of AMI patients.However,there is no significant relationship between IL-33 and the prognosis of AMI patients.展开更多
Objective:To investigat the diagnostic value of transient elastography combined with serum amyloid A and interleukin-6 in the degree of hepatitis B liver fibrosis.Methods:A total of 334 patients with chronic HBV infec...Objective:To investigat the diagnostic value of transient elastography combined with serum amyloid A and interleukin-6 in the degree of hepatitis B liver fibrosis.Methods:A total of 334 patients with chronic HBV infection that were admitted to the Department of Infectious Diseases of the First Affiliated Hospital of Hainan Medical College from January 2020 to May 2022 with informed consent and underwent liver biopsy puncture were selected.According to the pathological results,they were divided into no obvious fibrosis group,obvious fibrosis group and liver cirrhosis group.Comparison of liver stiffness measurement(LSM),serum amyloid A(SAA0,IL-6 levels between different groups.This study drawed was conducted draw the receiver operating characteristic(ROC)curve of each index to diagnose significant liver fibrosis and liver cirrhosis,and compared the area under the ROC curve(AUC)and diagnostic efficacy of each non-invasive fibrosis diagnostic model.The diagnostic performance of the combined assay was superior to that of APRI and FIB-4 In different degrees of liver fibrosis.Results:According to the degree of liver fibrosis,the levels of SAA,IL-6,and LSM in the no significant fibrosis group(n=140),the significant fibrosis group(n=134),and the cirrhosis group(n=60)were statistically significant difference(All P<0.001).SAA,IL-6 and LSM were significantly correlated with the degree of liver fibrosis(rs=0.456,rs=0.482,rs=0.602,All P<0.001).The AUC of SAA and IL-6 for the diagnosis of significant fibrosis in hepatitis B were 0.738 and 0.809,respectively.And the AUC for the diagnosis of liver cirrhosis were 0.813 and 0.823,respectively.The AUC for the combined diagnosis of significant fibrosis and cirrhosis were 0.930 and 0.964,respectively.The diagnostic performance of the combined assay was superior to that of APRI and FIB-4 in different degrees of liver fibrosis(All P<0.001).Conclusion:LSM combined with serum SAA and IL-6 has great diagnostic value for different degrees of hepatitis B liver fibrosis.展开更多
To study the effect of IL-18 and nitric oxide(NO) on the growth and metastasis of non-small cell lung cancer (NSCLC).Methods Serum IL-18 and nitrate and nitrite levels in 82 patients with NSCLC and 20 healthy control ...To study the effect of IL-18 and nitric oxide(NO) on the growth and metastasis of non-small cell lung cancer (NSCLC).Methods Serum IL-18 and nitrate and nitrite levels in 82 patients with NSCLC and 20 healthy control subjects were measured by using ELISA and Griess.Results The levels of serum IL-18 were (334.2±31.0)ng/L in NSCLC patients and (151.3±22.0)ng/L in control subjects,respectively.The levels of nitrate and nitrite were (237.1±21.0)μmol/L in NSCLC patients and (44.2±15.0)μmol/L in control subjects.The levels of serum IL-18 and nitrate and nitrite were not related with age,gender,histological types in patients with NSCLC.The levels of serum IL-18 was closely associated with TNM stage,lymph node metastasis and distal metastasis,but not with its degree and organ types of metastasis.There was a negative correlation between the levels of serum IL-18 and nitrate and nitrite.Conclusion Serum IL-18 and nitrate and nitrite levels may be useful to evaluate the prognosis of the patients with NSCLC.16 refs,2 tabs.展开更多
BACKGROUND: The IL-33/ST2 axis is involved in the pathogenesis of many diseases such as autoimmune diseases, cancer,and heart failure. However, studies of the IL-33/ST2 pathway in HBV-related acute-on-chronic liver f...BACKGROUND: The IL-33/ST2 axis is involved in the pathogenesis of many diseases such as autoimmune diseases, cancer,and heart failure. However, studies of the IL-33/ST2 pathway in HBV-related acute-on-chronic liver failure(HBV-ACLF) are lacking. The present study aimed to determine the prognostic role of serum IL-33/soluble ST2(s ST2) in HBV-ACLF.METHODS: Serum levels of IL-33 and sS T2 in healthy controls(HC, n=18), chronic hepatitis B(CHB, n=27) and HBV-ACLF(n=51) patients at the 1st and 4th week after enrollment were detected using ELISA, and clinical data were collected. The follow-up of HBV-ACLF patients lasted for 6 months at least.RESULTS: There was no significant difference of serum IL-33 level among HC, CHB and HBV-ACLF patients at week 1.However, serum s ST2 level differed significantly among the three groups: highest in the HBV-ACLF group, moderate in the CHB group and lowest in the HC group. There was a reverse correlation between serum s ST2 level and the survival of HBV-ACLF patients. The level of serum s ST2 in HBV-ACLF survivors was significantly declined from week 1 to week 4 following the treatment, whereas that in HBV-ACLF nonsurvivors remained at a high level during the same period. Furthermore, serum sS T2 level was significantly correlated with laboratory parameters and the most updated prognostic scores(CLIF-C OF score, CLIF-C ACLF score and ACLF grades). Thereceiver operating characteristics curves demonstrated that serum sS T2 level was a good diagnostic marker for predicting the 6-month mortality in HBV-ACLF patients, comparable to the most updated prognostic scores. Serum sS T2 cut-off points for predicting prognosis in HBV-ACLF patients were 76 ng/mL at week 1 or 53 ng/mL at week 4, respectively. HBV-ACLF patients with serum sS T2 level above the cut-off point often had a worse prognosis than those below the cut-off point.CONCLUSION: Serum s ST2 may act as a promising biomarker to assess severity and predict prognosis of patients with HBV-ACLF and help for the early identification and optimal treatment of HBV-ACLF patients at high risk of mortality.展开更多
BACKGROUND Acute pancreatitis(AP)is an inflammatory disease in which the regulatory pathway is complex and not well understood.Soluble suppression of tumorigenicity 2(sST2)protein receptor functions as a decoy recepto...BACKGROUND Acute pancreatitis(AP)is an inflammatory disease in which the regulatory pathway is complex and not well understood.Soluble suppression of tumorigenicity 2(sST2)protein receptor functions as a decoy receptor for interleukin(IL)-33 to prevent IL-33/suppression of tumorigenicity 2L(ST2L)-pathwaymediated T helper(Th)2 immune responses.AIM To investigate the role of sST2 in AP.METHODS We assessed the association between sST2 and severity of AP in 123 patients enrolled in this study.The serum levels of sST2,C-reactive protein(CRP)and Th1-and Th2-related cytokines,including interferon(IFN)-γ,tumor necrosis factor(TNF)-α,IL-2,IL-4,IL-5 and IL-13,were measured by highly sensitive ELISA,and the severity of AP in patients was evaluated by the 2012 Atlanta Classification Criteria.RESULTS Serum sST2 levels were significantly increased in AP patients,and further,these levels were significantly elevated in severe AP(SAP)patients compared to moderately severe AP(MSAP)and mild AP(MAP)patients.Logistic regression showed sST2 was a predictor of SAP[odds ratio(OR):1.003(1.001–1.006),P=0.000].sST2 cutoff point was 1190 pg/mL,and sST2 above this cutoff was associated with SAP.sST2 was also a predictor of any organ failure and mortality during AP[OR:1.006(1.003–1.009),P=0.000,OR:1.002(1.001–1.004),P=0.012,respectively].Additionally,the Th1-related cytokines IFN-γand TNF-αin the SAP group were higher and the Th2-related cytokine IL-4 in the SAP group was significantly lower than those in MSAP and MAP groups.CONCLUSION sST2 may be used as a novel inflammatory marker in predicting AP severity and may regulate the function and differentiation of IL-33/ST2-mediated Th1 and Th2 Lymphocytes in AP homeostasis.展开更多
Objective:To investigate the expression changes and clinical significance of Toll-like receptor-4(TLR-4)and interleukin-1β(IL-1β)in the serum and knee joint fluid in patients with knee osteoarthritis(KOA).Methods:Fr...Objective:To investigate the expression changes and clinical significance of Toll-like receptor-4(TLR-4)and interleukin-1β(IL-1β)in the serum and knee joint fluid in patients with knee osteoarthritis(KOA).Methods:From June 2017 to December 2018,220 cases of patients with KOA who were admitted in Department of Orthopedics of the Third Affiliated Hospital of Inner Mongolia Medical University(“our hospital”for short)were selected as the observation group.According to the severity of KOA,they were divided into the mild subgroup(n=98),the moderate subgroup(n=80)and the severe subgroup(n=42).In addition,60 cases of volunteers who received the physical examination in Health Medical Center of our hospital were selected as the control group.The levels of TLR-4 and IL-1βin the serum and knee joint fluid were detected by enzyme-linked immunosorbent assay,in order to analyze the correlation of TLR-4 and IL-1βlevels with the severity of KOA.Results:The levels of TLR-4 and IL-1βin the serum and knee joint fluid of the observation group were significantly higher than those of the control group,and the differences were statistically significant(all p<.05).The levels of TLR-4 and IL-1βin the serum and knee joint fluid of the severe subgroup were significantly higher than those of the mild subgroup and the moderate subgroup,and the levels of TLR-4 and IL-1βin the serum and knee joint fluid of the moderate subgroup were higher than those of the mild group.The differences were statistically significant(all p<.05).The levels of TLR-4 and IL-1βin the serum and knee joint fluid were positively correlated to the severity of KOA(r=.706,.729,.741,.715,all p<.05);in the serum,the level of TLR-4 was positively correlated to the level of IL-1β(r=.720,p<.05);in the joint fluid,the level of TLR-4 was positively correlated to the level of IL-1β(r=.736,p<.05).Conclusions:The levels of TLR-4 and IL-1βin the serum and knee joint fluid of KOA patients are abnormally increased,which is closely related with the severity of KOA.It can be used for clinical prediction,diagnosis and treatment of KOA.展开更多
Objective: Allergic airway diseases (AADs) are a group of heterogeneous disease mediated by T-helper type 2 (Th2) immune response and characterized with airway inflammation and remodeling, including allergic asth...Objective: Allergic airway diseases (AADs) are a group of heterogeneous disease mediated by T-helper type 2 (Th2) immune response and characterized with airway inflammation and remodeling, including allergic asthma, allergic rhinitis, and chronic rhinosinusitis with allergic background. This review aimed to discuss the abnormal epithelial-mesenchymal crosstalk in the pathogenesis of AADs. Data Sources: Articles referred in this review were collected from the database of PubMed published in English up to January 2018. Study Selection: We had done a literature search using the following terms "allergic airway disease OR asthma OR allergic rhinitis OR chronic sinusitis AND IL-25 OR IL-33 OR thymic stromal lymphopoietin OR fibrocyte". Related original or review articles were included and carefully analyzed. Results: It is now believed that abnormal epithelial-mesenchymal crosstalk underlies the pathogenesis of AADs. However, the key regulatory factors and molecular events involved in this process still remain unclear. Epithelium-derived triple cytokines, including interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP), are shown to act on various target cells and promote the Th2 immune response. Circulating fibrocyte is an important mesenchymal cell that can mediate tissue remodeling. We previously found that IL-25-circulating fibrocyte axis was significantly upregulated in patients with asthma, which may greatly contribute to asthmatic airway inflammation and remodeling. Conclusions: In view of the redundancy ofcytokines and "united airway" theory, we propose a new concept that IL-25/IL-33/TSLP-fibrocyte axis may play a vital role in the abnormal epithelial-mesenchymal crosstalk in some endotypes of AADs. This novel idea will guide potential new intervention schema for the common treatment of AADs sharing common pathogenesis in the future.展开更多
Background Interleukin (IL)-33 is a recently identified member of the IL-1 family that binds to the receptor, ST2L. This study examined IL-33 production in mouse liver and investigated its role in hepatic ischemia/r...Background Interleukin (IL)-33 is a recently identified member of the IL-1 family that binds to the receptor, ST2L. This study examined IL-33 production in mouse liver and investigated its role in hepatic ischemia/reperfusion (I/R) injury. Methods Male BALB/c mice ((22+3) g) were subjected to 90 minutes partial hepatic ischemia, followed by 6 hours reperfusion. First, mice were randomized into two groups: control group (laparotomy only, without blocking blood supply) and ischemia model group. IL-33 mRNA and serum protein levels were measured at 30, 60, 90 minutes after ischemia and 2 and 6 hours after reperfusion. Second, mice were randomized into four groups: control, model (injection of rabbit IgG polyclonal antibody), recombinant IL-33 intervention and anti-ST2L antibody intervention group. Mice were sacrificed 6 hours after reperfusion. Liver pathology was observed via transmission electron microscopy. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), IL-4, IL-5, IL-13, interferon-y (IFN-y) and tumor necrosis factor-a (TNF-a) levels were measured. Results Levels of IL-33 mRNA and protein did not change during ischemia (P 〉0.05) but increased significantly during reperfusion (P 〈0.05). After reperfusion for 6 hours, serum levels of ALT, AST, IL-4, IL-5, IL-13, IFN-~ and TNF-a were significantly increased (P 〈0.05), and hepatocellular ultrastructure was damaged. Pretreatment with IL-33 attenuated severity of liver damage compared with controls, but pretreatment with anti-ST2L antibody increased severity. Serum levels of IL-4, IL-5 and IL-13 protein increased whereas IFN-y decreased following IL-33 pretreatment. Pretreatment with anti-ST2L antibody significantly decreased serum IL-4, IL-5, IL-13 levels and increased serum IFN-r levels compared with controls (P 〈0.05). There was no change in the level of TNF-a. Conclusion IL-33 is produced systematically and locally in liver during I/R injury. Pretreatment with IL-33 is therapeutic for hepatic I/R injury, possibly via inducing a Thl to Th2 shift.展开更多
Interleukin-33(IL-33)is the most attractive novel cytokine identified as an IL-1 family member.IL-33 was first named NF-HEV(nuclear factor from high endothelial venules),as it was known to interact with nuclear chroma...Interleukin-33(IL-33)is the most attractive novel cytokine identified as an IL-1 family member.IL-33 was first named NF-HEV(nuclear factor from high endothelial venules),as it was known to interact with nuclear chromatin although its exact intracellular functions are still to be clarified.IL-33 is now recognized as the specific ligand for the orphan IL-1 receptor family member ST2 and to be involved in polarization of T cells towards T helper 2 cell phenotype and in activation of mast cells,bosophils,eosinophils and natural killer cells.It is essential for IL-33 to be extracellularly released in order to bind to the ST2 receptor and consequently play a crucial role in inflammatory,infectious and autoimmune diseases.However,like the IL-1 family members,IL-1b and IL-18,IL-33 mRNA is translated without a signal sequence for secretion.Additionally,IL-33 cannot be released by the processing and secretion mechanism shared by IL-1b and IL-18 as IL-33 is not a substrate of caspase-1 and does not require proteolysis for activation.In contrast,IL-33 can be inactivated by apoptotic caspases.Accordingly,IL-33 is proposed to be released as an alarmin from necrotic cells but to be deleted during apoptosis.Besides the known autocrine,paracrine,intracrine,juxtacrine and retrocrine mechanisms of cellular interaction with cytokines,release by necrotic cells is another pathway for a cytokine to display its function,which we suggest might be called‘necrocrine’.This mini review summarizes recent progress of how IL-33 displays potential immunoregulatory roles with a particular focus on its enigmatic production.展开更多
This is China’s pilot stndy in the assessment of the diagnostic value of serum soluble IL-2 receptor (sIL-2R) in gastric cancer.We measured its level by ELISA method in 45 patients with gastric cancer (without metast...This is China’s pilot stndy in the assessment of the diagnostic value of serum soluble IL-2 receptor (sIL-2R) in gastric cancer.We measured its level by ELISA method in 45 patients with gastric cancer (without metastasis:32;with metastasis:5;recurrence:8)27 gastric ulcer,展开更多
Sepsis remains a major clinical problem with high morbidity and mortality. As new inflammatory mediators are characterized, it is important to understand their roles in sepsis. Interleukin 33(IL-33) is a recently desc...Sepsis remains a major clinical problem with high morbidity and mortality. As new inflammatory mediators are characterized, it is important to understand their roles in sepsis. Interleukin 33(IL-33) is a recently described member of the IL-1 family that is widely expressed in cells of barrier tissues. Upon tissue damage, IL-33 is released as an alarmin and activates various types of cells of both the innate and adaptive immune system through binding to the ST2/IL-1 receptor accessory protein complex. IL-33 has apparent pleiotropic functions in many disease models, with its actions strongly shaped by the local microenvironment. Recent studies have established a role for the IL-33-ST2 axis in the initiation and perpetuation of inflammation during endotoxemia, but its roles in sepsis appear to be organism and model dependent. In this review, we focus on the recent advances in understanding the role of the IL-33/ST2 axis in sepsis.展开更多
Immune reactivity and chronic low-grade inflammation(metaflammation) play an important role in the pathogenesis of obesity-associated metabolic disorders, including type 2 diabetes and nonalcoholic fatty liver disease...Immune reactivity and chronic low-grade inflammation(metaflammation) play an important role in the pathogenesis of obesity-associated metabolic disorders, including type 2 diabetes and nonalcoholic fatty liver disease(NAFLD), a spectrum of diseases that include liver steatosis, nonalcoholic steatohepatitis(NASH), fibrosis, and cirrhosis. Increased adiposity and insulin resistance contribute to the progression from hepatic steatosis to NASH and fibrosis through the development of proinflammatory and profibrotic processes in the liver, including increased hepatic infiltration of innate and adaptive immune cells, altered balance of cytokines and chemokines, increased reactive oxygen species generation and hepatocellular death. Experimental models of dietary-induced NAFLD/NASH in mice on different genetic backgrounds or knockout mice with different immune reactivity are used for elucidating the pathogenesis of NASH and liver fibrosis. Galectin-3(Gal-3), a unique chimera-type β-galactoside-binding protein of the galectin family has a regulatory role in immunometabolism and fibrogenesis. Mice deficient in Gal-3 develop pronounced adiposity, hyperglycemia and hepatic steatosis, as well as attenuated liver inflammation and fibrosis when fed an obesogenic high-fat diet. Interleukin(IL)-33, a member of the IL-1 cytokine family, mediates its effects through the ST receptor, which is present on immune and nonimmune cells and participates in immunometabolic and fibrotic disorders. Recent evidence, including our own data, suggests a protective role for the IL-33/IL-33R(ST2) signaling pathway in obesity, adipose tissue inflammation and atherosclerosis, but a profibrotic role in NASH development. The link between Gal-3 and soluble ST2 in myocardial fibrosis and heart failure progression has been demonstrated and we have recently shown that Gal-3 and the IL-33/ST2 pathway interact and both have a profibrotic role in diet-induced NASH. This review discusses the current evidence on the roles of Gal-3 and the IL-33/ST2 pathway and their interplay in obesity-associated hepatic inflammation and fibrogenesis that may be of interest in the development of therapeutic interventions to prevent and/or reverse obesity-associated hepatic inflammation and fibrosis.展开更多
文摘Interleukin-18(IL-18) is a cytokine with many functions. This study was to investigate the serum levels of IL-18 and their clinical significance in patients with colore3ctaql carcinomas. Methods: Peripheral blood samples were obtained from 106 patients with colorectal carcinoma and 60 volunteers. The serum IL-18 levels were determined in each sample with an enzyme-linked immunosorbent assay (ELISA). Results: In patients before 1997, the mean IL-18 level was 338.46 pg/ml; in patients after 1997, the mean IL-18 level was 328.85 pg/ml, there is no evidence of loss of IL-18 immunoreactivity after prolonged storage at -80℃. The mean serum IL-18 level in 106 patients with colorectal carcinoma was significantly higher compared with the 60 healthy volunteers (P<0.05). Although the IL-18 level in patients with stage I did not differ from controls, the serum IL-18 levels of patients with stage II, stage III and stage IV disease were significantly higher compared with healthy control (P<0.05). The mean serum IL-18 level of patients with stage III disease, while the difference between patients with stage II and stage IV was not statistically significant (P>0.05). The survival rate of patients with IL-18 levels ≥346 pg/ml (n=47 patients) was significantly worse compared with patients who had IL-18 levels <346 pg/ml(n=57 patients). The 5-year-survival rates were 5.3% and 18.6%, respectively. Multivariate analysis using a Cox proportional hazards model identified the serum IL-18 level as an independent prognostic factor for survival Conclusion: The serum IL-18 level has a significant correlation with survival curve. The serum IL-18 level may represent a significant postoperative prognostic determinant in patients with colorectal carcinoma.
基金Supported by Ministry of Science and Technological Development of the Republic of Serbia(NO.175069)Faculty of Medical Sciences,University of Kragujevac(NO.JP15-05).
文摘Recent epidemiological and genetic studies have revealed an interconnection between schizophrenia and breast cancer.The mutual underlying pathophysiological mechanisms may be immunologically driven.A new cluster of molecules called alarmins may be involved in sterile brain inflammation,and we have already reported the potential impact of interleukin-33(IL-33)on positive symptoms onset and the role of its soluble trans-membranes full length receptor(sST2)on amelioration of negative symptoms in schizophrenia genesis.Furthermore,these molecules have already been shown to be involved in breast cancer etiopathogenesis.In this review article,we aim to describe the IL-33/suppressor of tumorigenicity 2(ST2)axis as a crossroad in schizophreniabreast cancer comorbidity.Considering that raloxifene could be tissue-specific and improve cognition and that tamoxifen resistance in breast carcinoma could be improved by strategies targeting IL-33,these selective estrogen receptor modulators could be useful in complementary treatment.These observations could guide further somatic,as well as psychiatric therapeutical protocols by incorporating what is known about immunity in schizophrenia.
文摘BACKGROUND As prevalence of nonalcoholic fatty liver disease increases in the population,livers with steatosis will continue to infiltrate the donor pool.Safe utilization of these extended criteria grafts is paramount given the increased risk associated with their use in transplantation.Prognostic factors that can predict liver dysfunction immediately after transplantation with macrosteatotic grafts are lacking.AIM To understand the relationship between interleukin-33(IL-33)and complement in recipients immediately following liver reperfusion as a marker of liver dysfunction.METHODS Cohort consisted of patients who received a liver transplant from September 2016–September 2019 at our institution.Clinical variables were retrospectively extracted from the electronic medical record.Back-table donor biopsies were obtained with donor steatosis percentage retrospectively determined by a boardcertified pathologist.Blood samples were available immediately following liver transplantation.Quantification of plasma IL-33 and complement proteins,C3a and C5a,were determined by enzyme-linked immunosorbent assay.For mRNA expression,RNA was extracted from donor biopsies and used against a 780 gene panel.RESULTS Cohort consisted of 99 donor and recipients.Donor median age was 45 years and 55%male.Recipients had a median age of 59 years with 62%male.The main etiologies were alcoholic hepatitis,nonalcoholic steatohepatitis,and hepatocellular carcinoma.Median MELD-Na at transplant was 21.Donors were grouped based on moderate macrosteatosis(≥30%).Recipients implanted with moderate macrosteatotic grafts had significantly higher peak alanine aminotransferase/aspartate aminotransferase(P<0.001 and P<0.004),and increased incidence of early allograft dysfunction(60%compared to 18%).Circulating IL-33 levels were significantly elevated in recipients of≥30%macrosteatotic grafts(P<0.05).Recipients with detectable levels of circulating IL-33 immediately following reperfusion had significantly higher alanine aminotransferase/aspartate aminotransferase(P<0.05 and P<0.01).Activated complement(C3a and C5a)were elevated in recipients implanted with moderate macrosteatotic grafts.RNA expression analysis of donor biopsies revealed moderate steatotic grafts upregulated genes inflammatory processes while downregulated hepatocyte-produced complement factors.CONCLUSION Circulating IL-33 and activated complement levels immediately following liver reperfusion in recipients of moderate macrosteatotic grafts may identify which patients are at risk of early allograft dysfunction.
基金National Natural Science Foundation of China(81801894,81760341)Basic Science and Frontier Technology Research Project of Chongqing Science and Technology Commission(cstc 2016jcyjA0005)+1 种基金Science and Technology Research Project of Chongqing Education Commission(KJ1702034)Traditional Chinese Medicine Science and Technology Project of Chongqing Health and Family Planning Commission(ZY201702071).
文摘Interleukin (IL) 33 is a key cytokine in type II immune and airway diseases. It is abundantly expressed in lung epithelial cells and plays an important role in both innate and adaptive immunity. In innate immunity, IL-33 responds promptly to produce an immune response that maintains homeostasis. In adaptive immunity, IL-33 interacts with various immune cells. At the same time, IL-33 also plays an important role in chronic inflammation of the airway and its remodeling. This article reviews the relevant biological knowledge of IL-33 and its research progress in lung immunity, and discusses the related issues of IL-33 as a lung immune test site and therapeutic target.
文摘Background Acute myocardial infarction (AMI) is a common cardiac emergency with high mortality.Serum soluble ST2 (sST2) is a new emerging biomarker of cardiac diseases.The present study is to investigate the predictive value of sST2 and interleukin-33 (IL-33) for risk stratification and prognosis in patients with AMI.Methods Fifty-nine patients with AMI,whose chief complaint was chest pain or dyspnea,were selected for our study.Physical examination,chest radiograph,electrocardiograph (ECG),biomarkers of myocardial infarction,NT-proBNP,echocardiography and other relevant examinations were performed to confirm the diagnosis of AMI.Thirty-six healthy people were chosen as the control group.Serum samples from these subjects (patients within 24 hours after acute attack) were collected and the levels of sST2 and IL-33 were assayed by enzyme-linked immuno-sorbent assay (ELISA) kit.The follow-up was performed on the 7th day,28th day,3rd month and 6th month after acute attack.According to the follow-up results we defined the end of observation as recurrence of AMI or any causes of death.Results Median sST2 level of the control group was 9.38ng/ml and that of AMI patients was 29.06ng/ml.Compared with the control group,sST2 expression in the AMI group was significantly different (P〈0.001).In contrast,the IL-33 level showed no significant difference between the two groups.Serum sST2 was a predictive factor independent of other variables and may provide complementary information to NT-proBNP or GRACE risk score.IL-33 had no relationship to recurrence of AMI.Both sST2 and the IL-33/sST2 ratio were correlated with the 6-month prognosis; areas under the ROC curve were 0.938 and 0.920 respectively.Conclusions Early in the course (〈24 hours) of AMI,sST2 usually increases markedly.The increase of sST2 has an independent predictive value for the prognosis in AMI patients and provides complementary information to NT-proBNP or GRACE risk score.The IL-33/sST2 ratio correlates with the 6-month prognosis of AMI patients.However,there is no significant relationship between IL-33 and the prognosis of AMI patients.
基金Natural Science Foundation of Hainan Province(No.819MS122)。
文摘Objective:To investigat the diagnostic value of transient elastography combined with serum amyloid A and interleukin-6 in the degree of hepatitis B liver fibrosis.Methods:A total of 334 patients with chronic HBV infection that were admitted to the Department of Infectious Diseases of the First Affiliated Hospital of Hainan Medical College from January 2020 to May 2022 with informed consent and underwent liver biopsy puncture were selected.According to the pathological results,they were divided into no obvious fibrosis group,obvious fibrosis group and liver cirrhosis group.Comparison of liver stiffness measurement(LSM),serum amyloid A(SAA0,IL-6 levels between different groups.This study drawed was conducted draw the receiver operating characteristic(ROC)curve of each index to diagnose significant liver fibrosis and liver cirrhosis,and compared the area under the ROC curve(AUC)and diagnostic efficacy of each non-invasive fibrosis diagnostic model.The diagnostic performance of the combined assay was superior to that of APRI and FIB-4 In different degrees of liver fibrosis.Results:According to the degree of liver fibrosis,the levels of SAA,IL-6,and LSM in the no significant fibrosis group(n=140),the significant fibrosis group(n=134),and the cirrhosis group(n=60)were statistically significant difference(All P<0.001).SAA,IL-6 and LSM were significantly correlated with the degree of liver fibrosis(rs=0.456,rs=0.482,rs=0.602,All P<0.001).The AUC of SAA and IL-6 for the diagnosis of significant fibrosis in hepatitis B were 0.738 and 0.809,respectively.And the AUC for the diagnosis of liver cirrhosis were 0.813 and 0.823,respectively.The AUC for the combined diagnosis of significant fibrosis and cirrhosis were 0.930 and 0.964,respectively.The diagnostic performance of the combined assay was superior to that of APRI and FIB-4 in different degrees of liver fibrosis(All P<0.001).Conclusion:LSM combined with serum SAA and IL-6 has great diagnostic value for different degrees of hepatitis B liver fibrosis.
文摘To study the effect of IL-18 and nitric oxide(NO) on the growth and metastasis of non-small cell lung cancer (NSCLC).Methods Serum IL-18 and nitrate and nitrite levels in 82 patients with NSCLC and 20 healthy control subjects were measured by using ELISA and Griess.Results The levels of serum IL-18 were (334.2±31.0)ng/L in NSCLC patients and (151.3±22.0)ng/L in control subjects,respectively.The levels of nitrate and nitrite were (237.1±21.0)μmol/L in NSCLC patients and (44.2±15.0)μmol/L in control subjects.The levels of serum IL-18 and nitrate and nitrite were not related with age,gender,histological types in patients with NSCLC.The levels of serum IL-18 was closely associated with TNM stage,lymph node metastasis and distal metastasis,but not with its degree and organ types of metastasis.There was a negative correlation between the levels of serum IL-18 and nitrate and nitrite.Conclusion Serum IL-18 and nitrate and nitrite levels may be useful to evaluate the prognosis of the patients with NSCLC.16 refs,2 tabs.
基金supported by grants from the National Natural Science Foundation of China(81300316 and 81570535)the National Key Programs on Infectious Diseases of China(2012ZX10002004-003)+2 种基金the National Clinical Key Speciality Construction Project of China(Infectious Diseases)Shanghai Public Health Three-Year Action Project(15GWZK0102)Project of Shanghai Municipal Health and Family Planning(20144329)
文摘BACKGROUND: The IL-33/ST2 axis is involved in the pathogenesis of many diseases such as autoimmune diseases, cancer,and heart failure. However, studies of the IL-33/ST2 pathway in HBV-related acute-on-chronic liver failure(HBV-ACLF) are lacking. The present study aimed to determine the prognostic role of serum IL-33/soluble ST2(s ST2) in HBV-ACLF.METHODS: Serum levels of IL-33 and sS T2 in healthy controls(HC, n=18), chronic hepatitis B(CHB, n=27) and HBV-ACLF(n=51) patients at the 1st and 4th week after enrollment were detected using ELISA, and clinical data were collected. The follow-up of HBV-ACLF patients lasted for 6 months at least.RESULTS: There was no significant difference of serum IL-33 level among HC, CHB and HBV-ACLF patients at week 1.However, serum s ST2 level differed significantly among the three groups: highest in the HBV-ACLF group, moderate in the CHB group and lowest in the HC group. There was a reverse correlation between serum s ST2 level and the survival of HBV-ACLF patients. The level of serum s ST2 in HBV-ACLF survivors was significantly declined from week 1 to week 4 following the treatment, whereas that in HBV-ACLF nonsurvivors remained at a high level during the same period. Furthermore, serum sS T2 level was significantly correlated with laboratory parameters and the most updated prognostic scores(CLIF-C OF score, CLIF-C ACLF score and ACLF grades). Thereceiver operating characteristics curves demonstrated that serum sS T2 level was a good diagnostic marker for predicting the 6-month mortality in HBV-ACLF patients, comparable to the most updated prognostic scores. Serum sS T2 cut-off points for predicting prognosis in HBV-ACLF patients were 76 ng/mL at week 1 or 53 ng/mL at week 4, respectively. HBV-ACLF patients with serum sS T2 level above the cut-off point often had a worse prognosis than those below the cut-off point.CONCLUSION: Serum s ST2 may act as a promising biomarker to assess severity and predict prognosis of patients with HBV-ACLF and help for the early identification and optimal treatment of HBV-ACLF patients at high risk of mortality.
基金Supported by Henan Province Education Department for Henan Province University Key Scientific Research Project,No.20A320018 and No.20A320064。
文摘BACKGROUND Acute pancreatitis(AP)is an inflammatory disease in which the regulatory pathway is complex and not well understood.Soluble suppression of tumorigenicity 2(sST2)protein receptor functions as a decoy receptor for interleukin(IL)-33 to prevent IL-33/suppression of tumorigenicity 2L(ST2L)-pathwaymediated T helper(Th)2 immune responses.AIM To investigate the role of sST2 in AP.METHODS We assessed the association between sST2 and severity of AP in 123 patients enrolled in this study.The serum levels of sST2,C-reactive protein(CRP)and Th1-and Th2-related cytokines,including interferon(IFN)-γ,tumor necrosis factor(TNF)-α,IL-2,IL-4,IL-5 and IL-13,were measured by highly sensitive ELISA,and the severity of AP in patients was evaluated by the 2012 Atlanta Classification Criteria.RESULTS Serum sST2 levels were significantly increased in AP patients,and further,these levels were significantly elevated in severe AP(SAP)patients compared to moderately severe AP(MSAP)and mild AP(MAP)patients.Logistic regression showed sST2 was a predictor of SAP[odds ratio(OR):1.003(1.001–1.006),P=0.000].sST2 cutoff point was 1190 pg/mL,and sST2 above this cutoff was associated with SAP.sST2 was also a predictor of any organ failure and mortality during AP[OR:1.006(1.003–1.009),P=0.000,OR:1.002(1.001–1.004),P=0.012,respectively].Additionally,the Th1-related cytokines IFN-γand TNF-αin the SAP group were higher and the Th2-related cytokine IL-4 in the SAP group was significantly lower than those in MSAP and MAP groups.CONCLUSION sST2 may be used as a novel inflammatory marker in predicting AP severity and may regulate the function and differentiation of IL-33/ST2-mediated Th1 and Th2 Lymphocytes in AP homeostasis.
文摘Objective:To investigate the expression changes and clinical significance of Toll-like receptor-4(TLR-4)and interleukin-1β(IL-1β)in the serum and knee joint fluid in patients with knee osteoarthritis(KOA).Methods:From June 2017 to December 2018,220 cases of patients with KOA who were admitted in Department of Orthopedics of the Third Affiliated Hospital of Inner Mongolia Medical University(“our hospital”for short)were selected as the observation group.According to the severity of KOA,they were divided into the mild subgroup(n=98),the moderate subgroup(n=80)and the severe subgroup(n=42).In addition,60 cases of volunteers who received the physical examination in Health Medical Center of our hospital were selected as the control group.The levels of TLR-4 and IL-1βin the serum and knee joint fluid were detected by enzyme-linked immunosorbent assay,in order to analyze the correlation of TLR-4 and IL-1βlevels with the severity of KOA.Results:The levels of TLR-4 and IL-1βin the serum and knee joint fluid of the observation group were significantly higher than those of the control group,and the differences were statistically significant(all p<.05).The levels of TLR-4 and IL-1βin the serum and knee joint fluid of the severe subgroup were significantly higher than those of the mild subgroup and the moderate subgroup,and the levels of TLR-4 and IL-1βin the serum and knee joint fluid of the moderate subgroup were higher than those of the mild group.The differences were statistically significant(all p<.05).The levels of TLR-4 and IL-1βin the serum and knee joint fluid were positively correlated to the severity of KOA(r=.706,.729,.741,.715,all p<.05);in the serum,the level of TLR-4 was positively correlated to the level of IL-1β(r=.720,p<.05);in the joint fluid,the level of TLR-4 was positively correlated to the level of IL-1β(r=.736,p<.05).Conclusions:The levels of TLR-4 and IL-1βin the serum and knee joint fluid of KOA patients are abnormally increased,which is closely related with the severity of KOA.It can be used for clinical prediction,diagnosis and treatment of KOA.
基金This study was supported by grants from the Natural Science Foundation of China (No. 81641003) and Application of Clinical Features in Capital City by the Beijing Municipal Science and Technology Commission (No. Z131107002213135).
文摘Objective: Allergic airway diseases (AADs) are a group of heterogeneous disease mediated by T-helper type 2 (Th2) immune response and characterized with airway inflammation and remodeling, including allergic asthma, allergic rhinitis, and chronic rhinosinusitis with allergic background. This review aimed to discuss the abnormal epithelial-mesenchymal crosstalk in the pathogenesis of AADs. Data Sources: Articles referred in this review were collected from the database of PubMed published in English up to January 2018. Study Selection: We had done a literature search using the following terms "allergic airway disease OR asthma OR allergic rhinitis OR chronic sinusitis AND IL-25 OR IL-33 OR thymic stromal lymphopoietin OR fibrocyte". Related original or review articles were included and carefully analyzed. Results: It is now believed that abnormal epithelial-mesenchymal crosstalk underlies the pathogenesis of AADs. However, the key regulatory factors and molecular events involved in this process still remain unclear. Epithelium-derived triple cytokines, including interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP), are shown to act on various target cells and promote the Th2 immune response. Circulating fibrocyte is an important mesenchymal cell that can mediate tissue remodeling. We previously found that IL-25-circulating fibrocyte axis was significantly upregulated in patients with asthma, which may greatly contribute to asthmatic airway inflammation and remodeling. Conclusions: In view of the redundancy ofcytokines and "united airway" theory, we propose a new concept that IL-25/IL-33/TSLP-fibrocyte axis may play a vital role in the abnormal epithelial-mesenchymal crosstalk in some endotypes of AADs. This novel idea will guide potential new intervention schema for the common treatment of AADs sharing common pathogenesis in the future.
文摘Background Interleukin (IL)-33 is a recently identified member of the IL-1 family that binds to the receptor, ST2L. This study examined IL-33 production in mouse liver and investigated its role in hepatic ischemia/reperfusion (I/R) injury. Methods Male BALB/c mice ((22+3) g) were subjected to 90 minutes partial hepatic ischemia, followed by 6 hours reperfusion. First, mice were randomized into two groups: control group (laparotomy only, without blocking blood supply) and ischemia model group. IL-33 mRNA and serum protein levels were measured at 30, 60, 90 minutes after ischemia and 2 and 6 hours after reperfusion. Second, mice were randomized into four groups: control, model (injection of rabbit IgG polyclonal antibody), recombinant IL-33 intervention and anti-ST2L antibody intervention group. Mice were sacrificed 6 hours after reperfusion. Liver pathology was observed via transmission electron microscopy. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), IL-4, IL-5, IL-13, interferon-y (IFN-y) and tumor necrosis factor-a (TNF-a) levels were measured. Results Levels of IL-33 mRNA and protein did not change during ischemia (P 〉0.05) but increased significantly during reperfusion (P 〈0.05). After reperfusion for 6 hours, serum levels of ALT, AST, IL-4, IL-5, IL-13, IFN-~ and TNF-a were significantly increased (P 〈0.05), and hepatocellular ultrastructure was damaged. Pretreatment with IL-33 attenuated severity of liver damage compared with controls, but pretreatment with anti-ST2L antibody increased severity. Serum levels of IL-4, IL-5 and IL-13 protein increased whereas IFN-y decreased following IL-33 pretreatment. Pretreatment with anti-ST2L antibody significantly decreased serum IL-4, IL-5, IL-13 levels and increased serum IFN-r levels compared with controls (P 〈0.05). There was no change in the level of TNF-a. Conclusion IL-33 is produced systematically and locally in liver during I/R injury. Pretreatment with IL-33 is therapeutic for hepatic I/R injury, possibly via inducing a Thl to Th2 shift.
文摘Interleukin-33(IL-33)is the most attractive novel cytokine identified as an IL-1 family member.IL-33 was first named NF-HEV(nuclear factor from high endothelial venules),as it was known to interact with nuclear chromatin although its exact intracellular functions are still to be clarified.IL-33 is now recognized as the specific ligand for the orphan IL-1 receptor family member ST2 and to be involved in polarization of T cells towards T helper 2 cell phenotype and in activation of mast cells,bosophils,eosinophils and natural killer cells.It is essential for IL-33 to be extracellularly released in order to bind to the ST2 receptor and consequently play a crucial role in inflammatory,infectious and autoimmune diseases.However,like the IL-1 family members,IL-1b and IL-18,IL-33 mRNA is translated without a signal sequence for secretion.Additionally,IL-33 cannot be released by the processing and secretion mechanism shared by IL-1b and IL-18 as IL-33 is not a substrate of caspase-1 and does not require proteolysis for activation.In contrast,IL-33 can be inactivated by apoptotic caspases.Accordingly,IL-33 is proposed to be released as an alarmin from necrotic cells but to be deleted during apoptosis.Besides the known autocrine,paracrine,intracrine,juxtacrine and retrocrine mechanisms of cellular interaction with cytokines,release by necrotic cells is another pathway for a cytokine to display its function,which we suggest might be called‘necrocrine’.This mini review summarizes recent progress of how IL-33 displays potential immunoregulatory roles with a particular focus on its enigmatic production.
文摘This is China’s pilot stndy in the assessment of the diagnostic value of serum soluble IL-2 receptor (sIL-2R) in gastric cancer.We measured its level by ELISA method in 45 patients with gastric cancer (without metastasis:32;with metastasis:5;recurrence:8)27 gastric ulcer,
基金supported by the National Institutes of Health(RO1-GM 044100,RO1-GM 050441)
文摘Sepsis remains a major clinical problem with high morbidity and mortality. As new inflammatory mediators are characterized, it is important to understand their roles in sepsis. Interleukin 33(IL-33) is a recently described member of the IL-1 family that is widely expressed in cells of barrier tissues. Upon tissue damage, IL-33 is released as an alarmin and activates various types of cells of both the innate and adaptive immune system through binding to the ST2/IL-1 receptor accessory protein complex. IL-33 has apparent pleiotropic functions in many disease models, with its actions strongly shaped by the local microenvironment. Recent studies have established a role for the IL-33-ST2 axis in the initiation and perpetuation of inflammation during endotoxemia, but its roles in sepsis appear to be organism and model dependent. In this review, we focus on the recent advances in understanding the role of the IL-33/ST2 axis in sepsis.
基金Supported by Swiss Science Foundation,No.SCOPES,IZ73Z0_152407
文摘Immune reactivity and chronic low-grade inflammation(metaflammation) play an important role in the pathogenesis of obesity-associated metabolic disorders, including type 2 diabetes and nonalcoholic fatty liver disease(NAFLD), a spectrum of diseases that include liver steatosis, nonalcoholic steatohepatitis(NASH), fibrosis, and cirrhosis. Increased adiposity and insulin resistance contribute to the progression from hepatic steatosis to NASH and fibrosis through the development of proinflammatory and profibrotic processes in the liver, including increased hepatic infiltration of innate and adaptive immune cells, altered balance of cytokines and chemokines, increased reactive oxygen species generation and hepatocellular death. Experimental models of dietary-induced NAFLD/NASH in mice on different genetic backgrounds or knockout mice with different immune reactivity are used for elucidating the pathogenesis of NASH and liver fibrosis. Galectin-3(Gal-3), a unique chimera-type β-galactoside-binding protein of the galectin family has a regulatory role in immunometabolism and fibrogenesis. Mice deficient in Gal-3 develop pronounced adiposity, hyperglycemia and hepatic steatosis, as well as attenuated liver inflammation and fibrosis when fed an obesogenic high-fat diet. Interleukin(IL)-33, a member of the IL-1 cytokine family, mediates its effects through the ST receptor, which is present on immune and nonimmune cells and participates in immunometabolic and fibrotic disorders. Recent evidence, including our own data, suggests a protective role for the IL-33/IL-33R(ST2) signaling pathway in obesity, adipose tissue inflammation and atherosclerosis, but a profibrotic role in NASH development. The link between Gal-3 and soluble ST2 in myocardial fibrosis and heart failure progression has been demonstrated and we have recently shown that Gal-3 and the IL-33/ST2 pathway interact and both have a profibrotic role in diet-induced NASH. This review discusses the current evidence on the roles of Gal-3 and the IL-33/ST2 pathway and their interplay in obesity-associated hepatic inflammation and fibrogenesis that may be of interest in the development of therapeutic interventions to prevent and/or reverse obesity-associated hepatic inflammation and fibrosis.