Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,...Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,IL-6,IL-8,IL-10,IL-12,and IL-17 families.Here,we review the functions of ILs in the pathogenesis and resolution of liver diseases,such as liver inflammation(e.g.,IL-35),alcoholrelated liver disease(e.g.,IL-11),non-alcoholic steatohepatitis(e.g.,IL-22),liver fibrosis(e.g.,Il-17a),and liver cancer(e.g.,IL-8).Overall,IL-1 family members are implicated in liver inflammation induced by different etiologies,such as alcohol consumption,high-fat diet,and hepatitis viruses.IL-2 family members mainly regulate T lymphocyte and NK cell proliferation and activation,and the differentiation of T cells.IL-6 family cytokines play important roles in acute phase response in liver infection,liver regeneration,and metabolic regulation,as well as lymphocyte activation.IL-8,also known as CXCL8,is activated in chronic liver diseases,which is associated with the accumulation of neutrophils and macrophages.IL-10 family members contribute key roles to liver immune tolerance and immunosuppression in liver disease.IL-12 family cytokines influence T-cell differentiation and play an essential role in autoimmune liver disease.IL-17 subfamilies contribute to infection defense,liver inflammation,and Th17 cell differentiation.ILs interact with different type I and type II cytokine receptors to regulate intracellular signaling pathways that mediate their functions.However,most clinical studies are only performed to evaluate IL-mediated therapies on alcohol and hepatitis virus infection-induced hepatitis.More pre-clinical and clinical studies are required to evaluate IL-mediated monotherapy and synergistic therapies.展开更多
BACKGROUND Accumulating evidence suggests that the inflammatory cytokine interleukin-6(IL-6)contributes to the pathophysiology of psychiatric disorders.However,there was no study concerning the relationship between IL...BACKGROUND Accumulating evidence suggests that the inflammatory cytokine interleukin-6(IL-6)contributes to the pathophysiology of psychiatric disorders.However,there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia(EOS).AIM To investigate the relationship between serum IL-6 concentration and the clinical features of EOS.METHODS We measured serum IL-6 Levels from 74 patients with chronic schizophrenia,including 33 with age at onset<21 years(EOS group)and 41 with onset≥21 years in[adult-onset schizophrenia(AOS)group],and from 41 healthy controls.Symptom severities were evaluated using the Positive and Negative Syndrome Scale(PANSS).RESULTS Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls(F=22.32,P<0.01),but did not differ significantly between EOS and AOS groups(P>0.05)after controlling for age,body mass index,and other covariates.Negative symptom scores were higher in the EOS group than the AOS group(F=6.199,P=0.015).Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score(r=-0.389,P=0.032)and avolition/asociality subscore(r=-0.387,P=0.026).CONCLUSION Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness.IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.展开更多
Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not complet...Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.展开更多
Rheumatoid arthritis(RA) is an autoimmune disease, resulting in a chronic, systemic inflammatory disorder. It may affect many tissues and organs, but it primarily affects the flexible joints. In clinical practice pati...Rheumatoid arthritis(RA) is an autoimmune disease, resulting in a chronic, systemic inflammatory disorder. It may affect many tissues and organs, but it primarily affects the flexible joints. In clinical practice patient care generates many questions about diagnosis, prognosis, and treatment. It is challenging for health care specialists to keep up to date with the medical literature. This review summarizes the pathogenesis, the polymorphisms of interleukin and interleukin genes and the standard available and possible future immunologictargets for RA treatment. The identification of diseaseassociated interleukin and interleukin receptor genes can provide precious insight into the genetic variations prior to disease onset in order to identify the pathways important for RA pathogenesis. The knowledge of the complex genetic background may prove useful for developing novel therapies and making personalized medicine based on the individual's genetics.展开更多
Background and Objective: Previous research has speculated on the role of pro- and inflammatory immune mediators in the etiologic process of fatigue, with contrasting findings. The preponderance of the evidence suppor...Background and Objective: Previous research has speculated on the role of pro- and inflammatory immune mediators in the etiologic process of fatigue, with contrasting findings. The preponderance of the evidence supports the role of inflammatory mediators in the disease process of Chronic Fatigue Syndrome (CFS). The purpose of this study was to evaluate the production of interleukin (IL)-8 by peripheral blood mononuclear cells derived from individuals with chronic fatigue. A secondary objective was to determine if there was a significant relationship between IL-8 production and plasma cortisol level. Materials and Methodology: Data was collected from three groups, a sample of individuals with CFS (n = 15), a comparison sample of individuals with fatigue that did not meet criteria for CFS (n = 30) and a group of putatively health normative controls (n = 23). Peripheral blood was drawn and plasma samples derived. Peripheral blood mononuclear cells were stimulated with a mitogenic protocol and levels of IL8 in unstimulated and stimulated bulk supernatant determined. Results: Both fatigue groups displayed significantly higher levels of IL8 than the control group. The CFS group demonstrated higher levels of IL8 in plasma than the fatigue comparison group. Conclusion: The findings demonstrate a clear association between fatigue and IL8. The ability to identify an inflammatory marker in association with fatigue could provide a means of identifying those who may be at risk for the development of this disorder.展开更多
Seahorse embryos are brooded in the enclosed nutrient-rich environment of the male brood pouch,which may be prone to bacterial infection.The immune responses of interleukin(IL)genes in the brood pouch have not been we...Seahorse embryos are brooded in the enclosed nutrient-rich environment of the male brood pouch,which may be prone to bacterial infection.The immune responses of interleukin(IL)genes in the brood pouch have not been well studied.We identifi ed 13 interleukins in the lined seahorse Hippocampus erectus.Tissue-specifi c expression analysis revealed increased mRNA expression levels of il-1β,il-18,and il-8 in the brood pouch.When challenged with lipopolysaccharide or Vibrio parahaemolyticus,il-1βand il-18 were active as part of the acute and chronic infl ammatory responses,respectively.Importantly,il-8 may be involved in powerful antibacterial immune responses and may be induced by il-1βand il-18 via a process involving the nuclear factor-κB signaling pathway.These results suggest that il-1β,il-18,and il-8 may play key roles in the antibacterial immune defense of the brood pouch in male seahorses.展开更多
Inflammatory reactions in the gastrointestinal tract play an important role in the pathogenesis of gastroenteritis in bovine helminthosis. This study determined the serum concentrations of cytokines induced acute phas...Inflammatory reactions in the gastrointestinal tract play an important role in the pathogenesis of gastroenteritis in bovine helminthosis. This study determined the serum concentrations of cytokines induced acute phase proteins (Serum Amyloid A (SAA), Haptoglobin (Hp) and C-reactive protein (CRP)) and the levels of immunoreactive interleukins (IL-1, IL-2, IL-3, IL-4, IL-5 and IL-6) in cattle naturally infected with helminths. We sampled a total of 480 slaughtered cattle of both sexes in a major abattoir in Ibadan, Nigeria. Sedimentation, floatation and modified McMaster techniques were employed to determine the degrees of helminth infections. Animals with eggs per gram (epg) less than 200 were adjudged to be apparently healthy. The serum concentrations of interleukins and acute phase proteins were determined using the Technicon AutoAnalyzer Model AA II. It was found that mean SAA (μg/l) and CRP (%) levels were significantly (P 0.05). Therefore, some acute phase proteins are involved in the pathophysiology of bovine helminthosis and are closely related to the inflammatory activation of the disease. In lieu of these findings, it is suggested that systemic markers of inflammation can identify subjects at high risk of natural bovine helminthosis and that IL-6 and SAA may be used as indicators for bovine helminthosis.展开更多
BACKGROUND Gastric cancer(GC) is one of the most common malignancies in China with a high morbidity and mortality.AIM To determine whether interleukin(IL)-31, IL-32, and IL-33 can be used as biomarkers for the detecti...BACKGROUND Gastric cancer(GC) is one of the most common malignancies in China with a high morbidity and mortality.AIM To determine whether interleukin(IL)-31, IL-32, and IL-33 can be used as biomarkers for the detection of GC, via evaluating the correlations between their expression and clinicopathological parameters of GC patients.METHODS Tissue array(n = 180) gastric specimens were utilised. IL-31, IL-32, and IL-33 expression in GC and non-GC tissues was detected immunohistochemically. The correlations between IL-31, IL-32, and IL-33 expression in GC and severity of clinicopathological parameters were evaluated. Survival curves were plotted using the Kaplan-Meier method/Cox regression. Circulating IL-31, IL-32, and IL-33 were detected by ELISA.RESULTS We found that the expression levels of IL-31, IL-32, and IL-33 were all lower in GC than in adjacent non-GC gastric tissues(P < 0.05). IL-33 in peripheral blood of GC patients was significantly lower than that of healthy individuals(1.50 ± 1.11 vs 9.61 ± 8.00 ng/m L, P <0.05). Decreased IL-31, IL-32, and IL-33 in GC were observed in younger patients(< 60 years), and IL-32 and IL-33 were lower in female patients(P < 0.05). Higher IL-32 correlated with a longer survival in two GC subgroups: T4 invasion depth and TNM I-II stage. Univariate/multivariate analysis revealed that IL-32 was an independent prognostic factor for GC in the T4 stage subgroup. Circulating IL-33 was significantly lower in GC patients at TNM stage IV than in healthy people(P < 0.05).CONCLUSION Our findings may provide new insights into the roles of IL-31, IL-32, and IL-33 in the carcinogenesis of GC and demonstrate their relative usefulness as prognostic markers for GC. The underlying mechanism of IL-31, IL-32, and IL-33 actions in GC should be further explored.展开更多
The expression of interleukin-17 (IL-17) in lung and peripheral blood of asthmatic rats and the influence of dexamethasone, and the role of IL-17 in the pathogenesis of asthma were investigated. Thirty Sprague-Dawl...The expression of interleukin-17 (IL-17) in lung and peripheral blood of asthmatic rats and the influence of dexamethasone, and the role of IL-17 in the pathogenesis of asthma were investigated. Thirty Sprague-Dawley (SD) adult rats were randomly divided into three groups (n=10 in each group): normal group, asthmatic group, and dexamethasone-interfered group. Rat asthmatic model was established by intraperitoneal (i.p.) injection of 10% ovalbumin (OVA) and challenge with 1% OVA via inhalation. Rats in dexamethasone-interfered group were pretreated with dexamethasone (2 mg/kg, i.p.) 30 min before each challenge. The expression of IL-17 protein in serum and bronchoalveolar lavage fluid (BALF) was detected by ELISA. The expression of IL-17 mRNA in peripheral blood mononuclear cells (PBMC) and BALF cells was semi-quantitatively detected by RT-PCR. The expression of IL-17 protein in serum and BALF of asthmatic rats was significantly elevated as compared with normal rats and dexamethsone-interfered rats (P〈0.01), and there was significant difference between normal rats and dexamethsone-interfered rats (P〈0.05). The expression of IL-17 mRNA in PBMC and BALF cells of asthmatic rats was markedly increased as compared with normal rats and dexamethsone-interfered rats (P〈0.01), and significant difference was found between normal rats and dexamethsone-interfered rats (P〈0.05). It was concluded that the expression of IL-17 was increased significantly in asthmatic rats and could be inhibited partly by dexamethasone, suggesting that IL-17 might play an important role in the pathogenesis of asthma as an inflammation regulation factor.展开更多
Pigment epithelium-derived factor (PEDF) is an antiangiogenic factor which is effective in tumour inhibition in a variety of tumours and has not yet been studied in bladder tumour before. In this study the expressio...Pigment epithelium-derived factor (PEDF) is an antiangiogenic factor which is effective in tumour inhibition in a variety of tumours and has not yet been studied in bladder tumour before. In this study the expression of PEDF, interleukin-1α (IL-1α) and -8 (IL-8) in bladder tumours was investigated. Immunohistochemistry was performed on 64 bladder tumour and 23 normal uroepithelium samples. Expression change of the factors was compared with clinicopathological parameters. Correlations between PEDF, IL-1α and IL-8 were analyzed. None of the factors was in relation to gender, tumour occurrence, and size or onset pattern. PEDF (P=0.014) and IL-1α (P=0.049) expression was down-regulated with grade progression. PEDF expression was lower in normal uroepithelium than in papillary urothelial neoplasm of low malignant potential (PUNLMP) (P=0.000) and carcinoma (P=0.009) whilst IL-1α (P=0.000 and P=0.000 respectively) and IL-8 (P=0.000 and P=0.023 respectively) expression was higher in the same grouping. PEDF expression had a negative correlation with IL-8 in PUNLMP (P=0.049, r=-0.578) as well as in tumour grouping (P=0.033, r=-0.276). Deranged expressional change of PEDF, IL-1α and IL-8 could be in relation to loss of differentiation from normal uroepithelium to papillary lesion and eventually to carcinoma.展开更多
interleukin 12 (IL-12) is a powerful stimulus for the growth of activated T and natural killer cells,their generation of interferon γ(IFN-γ),and the differentiation of T helper type 1(Th1) effector cells from naive ...interleukin 12 (IL-12) is a powerful stimulus for the growth of activated T and natural killer cells,their generation of interferon γ(IFN-γ),and the differentiation of T helper type 1(Th1) effector cells from naive precursors in vitro. Using this characterized model of CD4 cell differentiation, we examined the immunologic effects of IL-12 administered either at the time of infection; when naive T cells are primed,or after 14 days of in fection,by which time CDt subset differentiation has occurred.Given with the inoculationof parasites,IL-12 induced IFN-γand IL-10 and markedly suppressed IL-4. Effects on IL10 and IL-4 are comparable in mice with homozygous disruption of the IFN-γgene (IFNγ%),and suppression of IL-4 was unchanged by administration of neutralizing anti-IL-10antibody.Induction of IFN-γand IL-10 mRNA by IL-12 also occurred in infected SCID mice.Given after day 14 of infection, however, IL-12 not only induced IFN-γand IL-10but also induced IL-4 in normal and IFN-γ% mice. These data demonstrate direct effects of IL-12 independent of IFN-γ IL-10,and IL-4 and demonstrate that the ineffectiveness of IL-12 administered following infection with Leishmania major correlates with resistance of differentiated Th2 cells to the IL-4 suppressing activity of IL-12.展开更多
A quantitative method using fluorescence spectro-photometer to detect theinterleukin 2 reocptor (IL 2R) on the surface of mononuclear cells in normal humanperipheral blood is described. For expression of IL 2R, the ...A quantitative method using fluorescence spectro-photometer to detect theinterleukin 2 reocptor (IL 2R) on the surface of mononuclear cells in normal humanperipheral blood is described. For expression of IL 2R, the optimum conoentration of PHA andCon A were 100 μg/ml and 10 μg/ml respectively. The PHA induced effect on mononuclear cellswas better than Con A induced one. The peak value of IL 2R cxpression was at the 24th h afterstimulation The optimum dilution of the first antibody (anti-Tac) was 1: 50, while the dilution ofthe second antibody(fluorescein conjugated rabbit anti-mousc IgG) was 1: 32 Their optimumincubation period was 20 and 10 min repectively. The concentration of fluorcscein-conjugatedantibody per 1×10<sup>6</sup> mononuclear cells from the same normal human peripheral blood was5.22±0.45×10<sup>-10</sup> mol, and the coefficient of variation was 8. 6%. The concentration offluorescein-conjugated antibody per 1×10<sup>6</sup>PBMC from five healthy individuals was 4. 8±0. 97×10<sup>-10</sup> mol Therefore this assay system is stable and quite reproducible.展开更多
The prognosis for patients with primarymalignant glioma remains poor, in spite of a varietyof different forms of treatments. Broad suppressionof humoral and cell-mediated immunity is found inpatients with malignant gl...The prognosis for patients with primarymalignant glioma remains poor, in spite of a varietyof different forms of treatments. Broad suppressionof humoral and cell-mediated immunity is found inpatients with malignant gliomas. Interleukin-2 (IL-2)production and IL-2 receptor expression are展开更多
AIM:To determine the involvement of the interleukin(IL)-6 with the development of experimental subretinal fibrosis in a mouse model.METHODS:Subretinal fibrosis was induced by subretinal injection of macrophage-rich pe...AIM:To determine the involvement of the interleukin(IL)-6 with the development of experimental subretinal fibrosis in a mouse model.METHODS:Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells and the local expression of IL-6 was assessed by quantitative real-time reverse transcriptionpolymerase chain reaction(RT-PCR)and enzyme-linked immunosorbent assay(ELISA)at various time points.In addition,we investigated the effect of IL-6 receptor(IL-6R)monoclonal antibody(MR16-1)on subretinal fibrosis development.RESULTS:IL-6 mRNA level was significantly elevated at 1d after subretinal fibrosis induction and increased further to about 12-fold at 2d,reaching the peak.The result of ELISA showed that IL-6 protein was not detected in naive mice.At 2d after subretinal fibrosis induction,IL-6 protein level was upregulated to 67.33±14.96 pg/mg in subretinal fibrosis mice.MR16-1treatment resulted in a reduced subretinal fibrosis area by 48%compared to animals from control group at 7d.CONCLUSION:Our results indicated that IL-6 signaling may contribute to the pathogenesis of subretinal fibrogenesis and IL-6R inhibition may provide an effective,novel treatment of advanced and late-stage neovascular age-related macular degeneration.展开更多
Objective: Monocytes/macrophages, proinflammatory cytokines and chemokines are important in the pathogenesis of glomerulonephritis. Interleukin (IL) -13 has been shown to exert potent anti-inflammatory properties. ...Objective: Monocytes/macrophages, proinflammatory cytokines and chemokines are important in the pathogenesis of glomerulonephritis. Interleukin (IL) -13 has been shown to exert potent anti-inflammatory properties. This study was designed to investigate the effect of IL-13 on the expression of proinflammatory cytokines, chemokines and profibrogenic cytokines and the involved molecular mechanism in cultured human mesangial cells (HMCs). Methods: The expressions of proinflammatory cytokines, chemokines and profibrogenic cytokines were determined by ribonuclease protection assay (RPA). Activity of nuclear factor-kappa B (NF-κB) and activa- tor protein-1 (AP-1) was examined by electrophoretic mobility shift assay (EMSA). NF-κB subunit p65 nuclear transportation and c-Jun N-terminal kinase (JNK) activity were assayed by immunoblot. Results: Recombinant IL-13 inhibited tumor necrosis factor-α (TNF-u), IL-1α, IL-1β, monocyte chemoattractant protein-1 (MCP-1), IL-8, and transforming growth factor-β1 (TGF-β1) mRNA expressions in a dose-dependent manner. Lipopoly- sacchorides (LPS) dramatically increased NF-κB DNA binding activity of HMCs, which was inhibited by IL-13 in a dose-dependent manner. LPS-activated NF-κB contained p50 and p65 dimers, but not c-Rel subunit. IL-13 blocked LPS-induced NF-κB subunit p65. LPS stimulated JNK/AP-1 activation, which was inhibited by IL-13 in a dose-dependent manner. Conclusion: IL-13 inhibits proinflammatory cytokines, chemokines, and profibrogenic cytokines synthesis by blocking NF-κB and JNK/AP-1 activation. These observations point to the importance of IL-13 in the modulation of inflammatory processes in the renal glomerulus.展开更多
Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effec...Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effects of aprotinin on them were observed. Twenty patients undergoing heart valve (s) replacement were randomly divided into two groups: control group (n=10) and apro- tinin group (n=10). In aprotinin group, 1 000 000 KIU aprotinin was given by vein injection and then 2 000 000 KIU was given as a bolus in prime. Blood samples were collected before CPB, right after CPB and on the 1st, 3rd and 7th postoperative day (POD) for serum IL-2 and sIL-2R determination. Results showed that after CPB, IL-2 was reduced and slL-2R increased. Meanwhile, serum IL-2R was lower in aprotinin group than that of control. It is concluded that the immunity depression after CPB is associated with low level of IL-2 and high level of sIL-2R and aprotinin can ameliorate the situation.展开更多
AIM:To clarify the current understanding of the association between interleukin-10(IL-10)polymorphisms and the risk of irritable bowel syndrome(IBS).METHODS:We searched for studies in any language recorded in PubMed,E...AIM:To clarify the current understanding of the association between interleukin-10(IL-10)polymorphisms and the risk of irritable bowel syndrome(IBS).METHODS:We searched for studies in any language recorded in PubMed,Embase and Cochrane library before August 2013.The associations under allele contrast model,codominant model,dominant model,and recessive model were analyzed.The strengths of the association between IL-10 polymorphisms and IBS risk were estimated using odds ratios(OR)with 95%confidence interval(CI).Fixed effects model was used to pool the result if the test of heterogeneity was not significant,otherwise the random-effect model was selected.RESULTS:Eight case-control studies analyzing three single-nucleotide polymorphisms rs1800870(-1082 A/G),rs1800871(-819C/T),and rs1800872(-592A/C)of the IL-10 gene,which involved 928 cases and 1363 controls,were eligible for our analysis.The results showed that rs1800870 polymorphisms were associated with a decreased risk of IBS(GG+GA vs AA:OR=0.80,95%CI:0.66-0.96),(AA+GA vs GG:OR=0.68,95%CI:0.52-0.90).Subgroup analysis revealed such association only existed in Caucasian ethnicity(AA+GA vs GG,OR=0.70,95%CI:0.55-0.89).The rs1800872 polymorphisms were associated with an increased risk of IBS in Asian ethnicity(CC vs GG:OR=1.29,95%CI:1.01-1.16).There were no associations between rs1800871 polymorphisms and the IBS risk.CONCLUSION:The results suggest that IL-10 rs1800870confers susceptibility to the risk of IBS in Caucasian ethnicity,and the rs1800872 may associate with IBS risk in Asians.However,no significant associations are found between rs1800871 and IBS risk.展开更多
文摘Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,IL-6,IL-8,IL-10,IL-12,and IL-17 families.Here,we review the functions of ILs in the pathogenesis and resolution of liver diseases,such as liver inflammation(e.g.,IL-35),alcoholrelated liver disease(e.g.,IL-11),non-alcoholic steatohepatitis(e.g.,IL-22),liver fibrosis(e.g.,Il-17a),and liver cancer(e.g.,IL-8).Overall,IL-1 family members are implicated in liver inflammation induced by different etiologies,such as alcohol consumption,high-fat diet,and hepatitis viruses.IL-2 family members mainly regulate T lymphocyte and NK cell proliferation and activation,and the differentiation of T cells.IL-6 family cytokines play important roles in acute phase response in liver infection,liver regeneration,and metabolic regulation,as well as lymphocyte activation.IL-8,also known as CXCL8,is activated in chronic liver diseases,which is associated with the accumulation of neutrophils and macrophages.IL-10 family members contribute key roles to liver immune tolerance and immunosuppression in liver disease.IL-12 family cytokines influence T-cell differentiation and play an essential role in autoimmune liver disease.IL-17 subfamilies contribute to infection defense,liver inflammation,and Th17 cell differentiation.ILs interact with different type I and type II cytokine receptors to regulate intracellular signaling pathways that mediate their functions.However,most clinical studies are only performed to evaluate IL-mediated therapies on alcohol and hepatitis virus infection-induced hepatitis.More pre-clinical and clinical studies are required to evaluate IL-mediated monotherapy and synergistic therapies.
基金Supported by National Natural Science Foundation of China,No.82371508 and No.81771439Jiangsu Provincial Key Research and Development Program,No.BE2020661+6 种基金Suzhou Municipal Health Commission Science Research Program,No.GSWS2020095National Mentorship Training Programme for Young Health Professionals,No.Qngg2022027Suzhou Clinical Key disciplines for Geriatric Psychiatry,No.SZXK202116Suzhou Clinical Medical Center for Mood Disorders,No.Szlcyxzx202109Suzhou Key Technologies Program,No.SKY2021063Suzhou Municipal Science and Technology Bureau Program,No.SKJY2021142,No.SKJY2021143,No.SKY2023227,No.SKY2022064 and No.SKYD2023159Suzhou Key Disease Diagnosis and Treatment Program,No.LCZX202218.
文摘BACKGROUND Accumulating evidence suggests that the inflammatory cytokine interleukin-6(IL-6)contributes to the pathophysiology of psychiatric disorders.However,there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia(EOS).AIM To investigate the relationship between serum IL-6 concentration and the clinical features of EOS.METHODS We measured serum IL-6 Levels from 74 patients with chronic schizophrenia,including 33 with age at onset<21 years(EOS group)and 41 with onset≥21 years in[adult-onset schizophrenia(AOS)group],and from 41 healthy controls.Symptom severities were evaluated using the Positive and Negative Syndrome Scale(PANSS).RESULTS Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls(F=22.32,P<0.01),but did not differ significantly between EOS and AOS groups(P>0.05)after controlling for age,body mass index,and other covariates.Negative symptom scores were higher in the EOS group than the AOS group(F=6.199,P=0.015).Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score(r=-0.389,P=0.032)and avolition/asociality subscore(r=-0.387,P=0.026).CONCLUSION Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness.IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.
基金supported by UniversitàCattolica(D1 intramural funds to RP)Italian Ministry of University and Research(PRIN 2022ZYLB7B,P2022YW7BP funds to CG).
文摘Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.
基金Supported by The Grant of the Hungarian Science Foundation,No.OTKA K103983
文摘Rheumatoid arthritis(RA) is an autoimmune disease, resulting in a chronic, systemic inflammatory disorder. It may affect many tissues and organs, but it primarily affects the flexible joints. In clinical practice patient care generates many questions about diagnosis, prognosis, and treatment. It is challenging for health care specialists to keep up to date with the medical literature. This review summarizes the pathogenesis, the polymorphisms of interleukin and interleukin genes and the standard available and possible future immunologictargets for RA treatment. The identification of diseaseassociated interleukin and interleukin receptor genes can provide precious insight into the genetic variations prior to disease onset in order to identify the pathways important for RA pathogenesis. The knowledge of the complex genetic background may prove useful for developing novel therapies and making personalized medicine based on the individual's genetics.
文摘Background and Objective: Previous research has speculated on the role of pro- and inflammatory immune mediators in the etiologic process of fatigue, with contrasting findings. The preponderance of the evidence supports the role of inflammatory mediators in the disease process of Chronic Fatigue Syndrome (CFS). The purpose of this study was to evaluate the production of interleukin (IL)-8 by peripheral blood mononuclear cells derived from individuals with chronic fatigue. A secondary objective was to determine if there was a significant relationship between IL-8 production and plasma cortisol level. Materials and Methodology: Data was collected from three groups, a sample of individuals with CFS (n = 15), a comparison sample of individuals with fatigue that did not meet criteria for CFS (n = 30) and a group of putatively health normative controls (n = 23). Peripheral blood was drawn and plasma samples derived. Peripheral blood mononuclear cells were stimulated with a mitogenic protocol and levels of IL8 in unstimulated and stimulated bulk supernatant determined. Results: Both fatigue groups displayed significantly higher levels of IL8 than the control group. The CFS group demonstrated higher levels of IL8 in plasma than the fatigue comparison group. Conclusion: The findings demonstrate a clear association between fatigue and IL8. The ability to identify an inflammatory marker in association with fatigue could provide a means of identifying those who may be at risk for the development of this disorder.
基金Supported by the National Science&Technology Fundamental Resources Investigation Program of China(No.2018FY100106),the National Natural Science Foundation of China(Nos.41825013,41806189)the Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)(No.GML2019ZD0407)the K.C.Wong Education Foundation,and the Guangdong Special Support Program of Leading Scientifi c and Technological Innovation(No.2017TX04N442)。
文摘Seahorse embryos are brooded in the enclosed nutrient-rich environment of the male brood pouch,which may be prone to bacterial infection.The immune responses of interleukin(IL)genes in the brood pouch have not been well studied.We identifi ed 13 interleukins in the lined seahorse Hippocampus erectus.Tissue-specifi c expression analysis revealed increased mRNA expression levels of il-1β,il-18,and il-8 in the brood pouch.When challenged with lipopolysaccharide or Vibrio parahaemolyticus,il-1βand il-18 were active as part of the acute and chronic infl ammatory responses,respectively.Importantly,il-8 may be involved in powerful antibacterial immune responses and may be induced by il-1βand il-18 via a process involving the nuclear factor-κB signaling pathway.These results suggest that il-1β,il-18,and il-8 may play key roles in the antibacterial immune defense of the brood pouch in male seahorses.
文摘Inflammatory reactions in the gastrointestinal tract play an important role in the pathogenesis of gastroenteritis in bovine helminthosis. This study determined the serum concentrations of cytokines induced acute phase proteins (Serum Amyloid A (SAA), Haptoglobin (Hp) and C-reactive protein (CRP)) and the levels of immunoreactive interleukins (IL-1, IL-2, IL-3, IL-4, IL-5 and IL-6) in cattle naturally infected with helminths. We sampled a total of 480 slaughtered cattle of both sexes in a major abattoir in Ibadan, Nigeria. Sedimentation, floatation and modified McMaster techniques were employed to determine the degrees of helminth infections. Animals with eggs per gram (epg) less than 200 were adjudged to be apparently healthy. The serum concentrations of interleukins and acute phase proteins were determined using the Technicon AutoAnalyzer Model AA II. It was found that mean SAA (μg/l) and CRP (%) levels were significantly (P 0.05). Therefore, some acute phase proteins are involved in the pathophysiology of bovine helminthosis and are closely related to the inflammatory activation of the disease. In lieu of these findings, it is suggested that systemic markers of inflammation can identify subjects at high risk of natural bovine helminthosis and that IL-6 and SAA may be used as indicators for bovine helminthosis.
基金Supported by the National Natural Science Foundation of China,No. 81502030。
文摘BACKGROUND Gastric cancer(GC) is one of the most common malignancies in China with a high morbidity and mortality.AIM To determine whether interleukin(IL)-31, IL-32, and IL-33 can be used as biomarkers for the detection of GC, via evaluating the correlations between their expression and clinicopathological parameters of GC patients.METHODS Tissue array(n = 180) gastric specimens were utilised. IL-31, IL-32, and IL-33 expression in GC and non-GC tissues was detected immunohistochemically. The correlations between IL-31, IL-32, and IL-33 expression in GC and severity of clinicopathological parameters were evaluated. Survival curves were plotted using the Kaplan-Meier method/Cox regression. Circulating IL-31, IL-32, and IL-33 were detected by ELISA.RESULTS We found that the expression levels of IL-31, IL-32, and IL-33 were all lower in GC than in adjacent non-GC gastric tissues(P < 0.05). IL-33 in peripheral blood of GC patients was significantly lower than that of healthy individuals(1.50 ± 1.11 vs 9.61 ± 8.00 ng/m L, P <0.05). Decreased IL-31, IL-32, and IL-33 in GC were observed in younger patients(< 60 years), and IL-32 and IL-33 were lower in female patients(P < 0.05). Higher IL-32 correlated with a longer survival in two GC subgroups: T4 invasion depth and TNM I-II stage. Univariate/multivariate analysis revealed that IL-32 was an independent prognostic factor for GC in the T4 stage subgroup. Circulating IL-33 was significantly lower in GC patients at TNM stage IV than in healthy people(P < 0.05).CONCLUSION Our findings may provide new insights into the roles of IL-31, IL-32, and IL-33 in the carcinogenesis of GC and demonstrate their relative usefulness as prognostic markers for GC. The underlying mechanism of IL-31, IL-32, and IL-33 actions in GC should be further explored.
文摘The expression of interleukin-17 (IL-17) in lung and peripheral blood of asthmatic rats and the influence of dexamethasone, and the role of IL-17 in the pathogenesis of asthma were investigated. Thirty Sprague-Dawley (SD) adult rats were randomly divided into three groups (n=10 in each group): normal group, asthmatic group, and dexamethasone-interfered group. Rat asthmatic model was established by intraperitoneal (i.p.) injection of 10% ovalbumin (OVA) and challenge with 1% OVA via inhalation. Rats in dexamethasone-interfered group were pretreated with dexamethasone (2 mg/kg, i.p.) 30 min before each challenge. The expression of IL-17 protein in serum and bronchoalveolar lavage fluid (BALF) was detected by ELISA. The expression of IL-17 mRNA in peripheral blood mononuclear cells (PBMC) and BALF cells was semi-quantitatively detected by RT-PCR. The expression of IL-17 protein in serum and BALF of asthmatic rats was significantly elevated as compared with normal rats and dexamethsone-interfered rats (P〈0.01), and there was significant difference between normal rats and dexamethsone-interfered rats (P〈0.05). The expression of IL-17 mRNA in PBMC and BALF cells of asthmatic rats was markedly increased as compared with normal rats and dexamethsone-interfered rats (P〈0.01), and significant difference was found between normal rats and dexamethsone-interfered rats (P〈0.05). It was concluded that the expression of IL-17 was increased significantly in asthmatic rats and could be inhibited partly by dexamethasone, suggesting that IL-17 might play an important role in the pathogenesis of asthma as an inflammation regulation factor.
基金sponsored in part by Science and Technology Commission of Shanghai Municipality, China (No. 07ZR14018)
文摘Pigment epithelium-derived factor (PEDF) is an antiangiogenic factor which is effective in tumour inhibition in a variety of tumours and has not yet been studied in bladder tumour before. In this study the expression of PEDF, interleukin-1α (IL-1α) and -8 (IL-8) in bladder tumours was investigated. Immunohistochemistry was performed on 64 bladder tumour and 23 normal uroepithelium samples. Expression change of the factors was compared with clinicopathological parameters. Correlations between PEDF, IL-1α and IL-8 were analyzed. None of the factors was in relation to gender, tumour occurrence, and size or onset pattern. PEDF (P=0.014) and IL-1α (P=0.049) expression was down-regulated with grade progression. PEDF expression was lower in normal uroepithelium than in papillary urothelial neoplasm of low malignant potential (PUNLMP) (P=0.000) and carcinoma (P=0.009) whilst IL-1α (P=0.000 and P=0.000 respectively) and IL-8 (P=0.000 and P=0.023 respectively) expression was higher in the same grouping. PEDF expression had a negative correlation with IL-8 in PUNLMP (P=0.049, r=-0.578) as well as in tumour grouping (P=0.033, r=-0.276). Deranged expressional change of PEDF, IL-1α and IL-8 could be in relation to loss of differentiation from normal uroepithelium to papillary lesion and eventually to carcinoma.
文摘interleukin 12 (IL-12) is a powerful stimulus for the growth of activated T and natural killer cells,their generation of interferon γ(IFN-γ),and the differentiation of T helper type 1(Th1) effector cells from naive precursors in vitro. Using this characterized model of CD4 cell differentiation, we examined the immunologic effects of IL-12 administered either at the time of infection; when naive T cells are primed,or after 14 days of in fection,by which time CDt subset differentiation has occurred.Given with the inoculationof parasites,IL-12 induced IFN-γand IL-10 and markedly suppressed IL-4. Effects on IL10 and IL-4 are comparable in mice with homozygous disruption of the IFN-γgene (IFNγ%),and suppression of IL-4 was unchanged by administration of neutralizing anti-IL-10antibody.Induction of IFN-γand IL-10 mRNA by IL-12 also occurred in infected SCID mice.Given after day 14 of infection, however, IL-12 not only induced IFN-γand IL-10but also induced IL-4 in normal and IFN-γ% mice. These data demonstrate direct effects of IL-12 independent of IFN-γ IL-10,and IL-4 and demonstrate that the ineffectiveness of IL-12 administered following infection with Leishmania major correlates with resistance of differentiated Th2 cells to the IL-4 suppressing activity of IL-12.
文摘A quantitative method using fluorescence spectro-photometer to detect theinterleukin 2 reocptor (IL 2R) on the surface of mononuclear cells in normal humanperipheral blood is described. For expression of IL 2R, the optimum conoentration of PHA andCon A were 100 μg/ml and 10 μg/ml respectively. The PHA induced effect on mononuclear cellswas better than Con A induced one. The peak value of IL 2R cxpression was at the 24th h afterstimulation The optimum dilution of the first antibody (anti-Tac) was 1: 50, while the dilution ofthe second antibody(fluorescein conjugated rabbit anti-mousc IgG) was 1: 32 Their optimumincubation period was 20 and 10 min repectively. The concentration of fluorcscein-conjugatedantibody per 1×10<sup>6</sup> mononuclear cells from the same normal human peripheral blood was5.22±0.45×10<sup>-10</sup> mol, and the coefficient of variation was 8. 6%. The concentration offluorescein-conjugated antibody per 1×10<sup>6</sup>PBMC from five healthy individuals was 4. 8±0. 97×10<sup>-10</sup> mol Therefore this assay system is stable and quite reproducible.
文摘The prognosis for patients with primarymalignant glioma remains poor, in spite of a varietyof different forms of treatments. Broad suppressionof humoral and cell-mediated immunity is found inpatients with malignant gliomas. Interleukin-2 (IL-2)production and IL-2 receptor expression are
基金Supported by Liaoning Science and Technology Project(No.2013225303)
文摘AIM:To determine the involvement of the interleukin(IL)-6 with the development of experimental subretinal fibrosis in a mouse model.METHODS:Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells and the local expression of IL-6 was assessed by quantitative real-time reverse transcriptionpolymerase chain reaction(RT-PCR)and enzyme-linked immunosorbent assay(ELISA)at various time points.In addition,we investigated the effect of IL-6 receptor(IL-6R)monoclonal antibody(MR16-1)on subretinal fibrosis development.RESULTS:IL-6 mRNA level was significantly elevated at 1d after subretinal fibrosis induction and increased further to about 12-fold at 2d,reaching the peak.The result of ELISA showed that IL-6 protein was not detected in naive mice.At 2d after subretinal fibrosis induction,IL-6 protein level was upregulated to 67.33±14.96 pg/mg in subretinal fibrosis mice.MR16-1treatment resulted in a reduced subretinal fibrosis area by 48%compared to animals from control group at 7d.CONCLUSION:Our results indicated that IL-6 signaling may contribute to the pathogenesis of subretinal fibrogenesis and IL-6R inhibition may provide an effective,novel treatment of advanced and late-stage neovascular age-related macular degeneration.
基金supported by grants from the National Natural Science Foundation of China(No.30872803 to Aihua Zhang,No.30772365 to Songming Huang)the Jiangsu Key Medical Talent Foundation(No.RC2007015 to Aihua Zhangthe Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry of China
文摘Objective: Monocytes/macrophages, proinflammatory cytokines and chemokines are important in the pathogenesis of glomerulonephritis. Interleukin (IL) -13 has been shown to exert potent anti-inflammatory properties. This study was designed to investigate the effect of IL-13 on the expression of proinflammatory cytokines, chemokines and profibrogenic cytokines and the involved molecular mechanism in cultured human mesangial cells (HMCs). Methods: The expressions of proinflammatory cytokines, chemokines and profibrogenic cytokines were determined by ribonuclease protection assay (RPA). Activity of nuclear factor-kappa B (NF-κB) and activa- tor protein-1 (AP-1) was examined by electrophoretic mobility shift assay (EMSA). NF-κB subunit p65 nuclear transportation and c-Jun N-terminal kinase (JNK) activity were assayed by immunoblot. Results: Recombinant IL-13 inhibited tumor necrosis factor-α (TNF-u), IL-1α, IL-1β, monocyte chemoattractant protein-1 (MCP-1), IL-8, and transforming growth factor-β1 (TGF-β1) mRNA expressions in a dose-dependent manner. Lipopoly- sacchorides (LPS) dramatically increased NF-κB DNA binding activity of HMCs, which was inhibited by IL-13 in a dose-dependent manner. LPS-activated NF-κB contained p50 and p65 dimers, but not c-Rel subunit. IL-13 blocked LPS-induced NF-κB subunit p65. LPS stimulated JNK/AP-1 activation, which was inhibited by IL-13 in a dose-dependent manner. Conclusion: IL-13 inhibits proinflammatory cytokines, chemokines, and profibrogenic cytokines synthesis by blocking NF-κB and JNK/AP-1 activation. These observations point to the importance of IL-13 in the modulation of inflammatory processes in the renal glomerulus.
基金a grant from the NationalNatural Science Foundation of China (No. 39270658).
文摘Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effects of aprotinin on them were observed. Twenty patients undergoing heart valve (s) replacement were randomly divided into two groups: control group (n=10) and apro- tinin group (n=10). In aprotinin group, 1 000 000 KIU aprotinin was given by vein injection and then 2 000 000 KIU was given as a bolus in prime. Blood samples were collected before CPB, right after CPB and on the 1st, 3rd and 7th postoperative day (POD) for serum IL-2 and sIL-2R determination. Results showed that after CPB, IL-2 was reduced and slL-2R increased. Meanwhile, serum IL-2R was lower in aprotinin group than that of control. It is concluded that the immunity depression after CPB is associated with low level of IL-2 and high level of sIL-2R and aprotinin can ameliorate the situation.
基金Supported by National Natural Science Foundation of China,No.81260083 and No.31360221
文摘AIM:To clarify the current understanding of the association between interleukin-10(IL-10)polymorphisms and the risk of irritable bowel syndrome(IBS).METHODS:We searched for studies in any language recorded in PubMed,Embase and Cochrane library before August 2013.The associations under allele contrast model,codominant model,dominant model,and recessive model were analyzed.The strengths of the association between IL-10 polymorphisms and IBS risk were estimated using odds ratios(OR)with 95%confidence interval(CI).Fixed effects model was used to pool the result if the test of heterogeneity was not significant,otherwise the random-effect model was selected.RESULTS:Eight case-control studies analyzing three single-nucleotide polymorphisms rs1800870(-1082 A/G),rs1800871(-819C/T),and rs1800872(-592A/C)of the IL-10 gene,which involved 928 cases and 1363 controls,were eligible for our analysis.The results showed that rs1800870 polymorphisms were associated with a decreased risk of IBS(GG+GA vs AA:OR=0.80,95%CI:0.66-0.96),(AA+GA vs GG:OR=0.68,95%CI:0.52-0.90).Subgroup analysis revealed such association only existed in Caucasian ethnicity(AA+GA vs GG,OR=0.70,95%CI:0.55-0.89).The rs1800872 polymorphisms were associated with an increased risk of IBS in Asian ethnicity(CC vs GG:OR=1.29,95%CI:1.01-1.16).There were no associations between rs1800871 polymorphisms and the IBS risk.CONCLUSION:The results suggest that IL-10 rs1800870confers susceptibility to the risk of IBS in Caucasian ethnicity,and the rs1800872 may associate with IBS risk in Asians.However,no significant associations are found between rs1800871 and IBS risk.