Systemic juvenile idiopathic arthritis–associated lung disease: A retrospective cohort study

BACKGROUND Lung damage in systemic juvenile arthritis(sJIA)is one of the contemporary topics in pediatric rheumatology.Several previous studies showed the severe course and fatal outcomes in some patients.The information about interstitial lung disease(ILD)in the sJIA is scarce and limited to a total of 100 cases.AIM To describe the features of sJIA patients with ILD in detail.METHODS In the present retrospective cohort study,information about 5 patients less than 18-years-old with sJIA and ILD were included.The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019.ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement.Macrophage activation syndrome(MAS)was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement.RESULTS The onset age of sJIA ranged from 1 year to 10 years.The time interval before ILD ranged from 1 mo to 3 years.The disease course was characterized by the prevalence of the systemic features above articular involvement,intensive rash(100%),persistent and very active MAS(hScore range:194-220)with transaminitis(100%),and respiratory symptoms(100%).Only 3 patients(60%)developed a clubbing phenomenon.All patients(100%)had pleural effusion and 4 patients(80%)had pericardial effusion at the disease onset.Two patients(40%)developed pulmonary arterial hypertension.Infusion-related reactions to tocilizumab were observed in 3(60%)of the patients.One patient with trisomy 21 had a fatal disease course.Half of the remaining patients had sJIA remission and 2 patients had improvement.Lung disease improved in 3 patients(75%),but 1 of them had initial deterioration of lung involvement.One patient who has not achieved the sJIA remission had the progressed course of ILD.No cases of hyper-eosinophilia were noted.Four patients(80%)received canakinumab and one(20%)tocilizumab at the last follow-up visit.CONCLUSION ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset.Extensive rash,serositis(especially pleuritis),full-blown MAS with transaminitis,lymphopenia,trisomy 21,eosinophilia,and biologic infusion reaction are the main predictors of ILD.The following studies are needed to find the predictors,pathogenesis,and treatment options,for preventing and treating the ILD in sJIA patients.

Interleukin-6 compared to the other Th17/Treg related cytokines in inflammatory bowel disease and colorectal cancer

BACKGROUND The connection between inflammatory bowel disease(IBD)and colorectal cancer(CRC)is well-established,as persistent intestinal inflammation plays a substantial role in both disorders.Cytokines may further influence the inflammation and the carcinogenesis process.AIM To compare cytokine patterns of active IBD patients with early and advanced CRC.METHODS Choosing a panel of cytokines crucial for Th17/Treg differentiation and behavior,in colon specimens,as mRNA biomarkers,and their serum protein levels.RESULTS We found a significant difference between higher gene expression of FoxP3,TGFb1,IL-10,and IL-23,and approximately equal level of IL-6 in CRC patients in comparison with IBD patients.After stratification of CRC patients,we found a significant difference in FoxP3,IL-10,IL-23,and IL-17A mRNA in early cases compared to IBD,and IL-23 alone in advanced CRC.The protein levels of the cytokines were significantly higher in CRC patients compared to IBD patients.CONCLUSION Our findings showed that IL-6 upregulation is essential for both IBD and CRC development until the upregulation of other Th17/Treg related genes(TGFb1,IL-10,IL-23,and transcription factor FoxP3)is a crucial primarily for CRC development.The significantly upregulated IL-6 could be a potential drug target for IBD and prevention of CRC development as well.

Predictive role of interleukin-6 and CAT score in mechanical ventilation in patients with chronic obstructive pulmonary disease at the acute exacerbation stage in the emergency department

BACKGROUND:The study aimed to evaluate the predictive role of interleukin-6(IL-6)and chronic obstructive pulmonary disease(COPD)assessment test(CAT)score in mechanical ventilation(MV)in COPD patients at the acute exacerbation stage in the emergency department(ED).METHODS:For a one-year period,among adult patients in the ED who met the criteria of acute exacerbation of COPD,158 who received MV within 48 hours after admission were compared to 294 who didn't require MV within the same period after admission.IL-6 level and CAT score were compared between the two groups.The predicted value of IL-6 and CAT score was assessed by logistic regression analysis and a receiver operating characteristic(ROC)curve.RESULTS:The IL-6 and CAT scores in the 158 MV patients were much higher than those without.IL-6 and CAT scores were independent predictors of MV within 48 hours using logistic regression analysis(IL-6:odds ratio[OR]1.053,95%confidence interval[CI]1.039–1.067,P<0.001;CAT score:OR 1.122,95%CI 1.086–1.159,P<0.001).The combination of IL-6 and CAT scores(area under ROC curve[AUC]0.826,95%CI 0.786–0.866,P<0.001)improved the accuracy of predicting MV within 48 hours when compared with IL-6(AUC 0.752,95%CI 0.703–0.800,P<0.001)and CAT scores alone(AUC 0.739,95%CI 0.692–0.786,P<0.001).The sensitivity and specificity were 69.6%,74.1%,75.32%and 63.6%,respectively.CONCLUSION:The combined of IL-6 and CAT scores is useful for evaluating the risk of COPD patients at acute exacerbation in ED,and can provide a predictive value for MV or not within 48 hours.

Clinical Implications of Tumor Necrosis Factor-Alpha, Interleukin-6 and Resistin in Coronary Artery Disease

Tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) are involved in the progression of coronary artery disease (CAD). The cytokines’ levels are associated with the severity of CAD. We have recently reported on the association of resistin, a relatively novel cytokine with the pathogenesis of cardiovascular disease (CVD). Although the inflammatory cytokines’ impact on atherosclerosis is widely accepted, yet some controversy exists regarding the involvement of these factors in atherogenesis. The current review highlights the potential association of TNF-alpha, IL-6 and resistin SNPs (single nucleotide polymorphisms) with CAD. Molecular genetics data along with the intracellular signaling cascade mechanisms may have important clinical implications in the treatment of CAD.

Interleukin-6 and its soluble receptor in patients with liver cirrhosis and hepatocellular carcinoma

AIM： To evaluate the immunohistochemical localization of interleukin-6 （IL-6） and IL-6 receptor （IL-6R） on tumor tissue specimens from patients with hepatocellular carcinoma （HCC） and the serum levels of IL-6 and sIL-6R in a group of patients with HCC as well as liver cirrhosis （LC） in a group of patients with LC alone and in a control group. METHODS： Three groups of subjects were studied： group Ⅰ （n =83） suffering from HCC and LC, group Ⅱ （n = 72） suffering from LC alone and group Ⅲ （n =42） as healthy controls. All patients had hepatitis C virus infection. Serum IL-6 and IL-6R levels were determined using a commercially available ELISA kit. Immunohistochemistry was performed using the streptavidin-biotin complex and rabbit polyclonal antibodies against IL-6 and IL-6R. RESULTS： Immunohistochemistry analysis showed a medium to strong cytoplasmic and membrane reactivity for IL-6 and IL-6R respectively, in at least 40% of cases of HCC, whereas liver cirrhosis patients and controls were negative for IL-6 or showed a very mild and focal dot-like cytoplasmic reaction for IL-6R. Serum IL-6 levels in HCC group were significantly higher than those in LC and control groups （P〈 0.0001）. There was no significant difference in sIL-6R concentrations among 3 groups. When the patients with HCC were divided into groups according to Okuda＇s classification, a significant serum increase of IL-6 and slL-6R level was observed from stage Ⅰ to stage Ⅲ （P〈0.02, P〈0.0005）. When HCC and LC patients were divided into 3 classes of cirrhosis severity according to Child-Pugh, values in HCC patients were significantly higher than those in LC patients for each corresponding class （P〈 0.01）. CONCLUSION： IL-6 serum levels in HCC patients are higher than those in LC patients and controls, suggesting an increased production of this cytokine by neoplastic cells, sIL-6R values are similar in all groups, increasing only in stage III HCC patients. These data suggest that they have a closer relationship with the neoplastic mass rather than with the residual functioning hepatic mass.

Association Between IL-6 （Interleukin-6） and Iron Status in Rheumatoid Arthritis Patients

The study was performed to determine whether the srum concentrations of IL （interleukin）-6 are elevated in patients with RA （rheumatoid arthritis） and to investigate the relationship between IL-6 levels and iron status in RA patients. 95 serum samples were obtained, 70 of them from patients with RA who had visited the department of Rheumatology at Al-Sadder medical city in Najaf governorate （Iraq） and 25 age and sex-matched healthy controls. The authors assessed the clinical parameters of the disease, including ESR （erythrocyte sedimentation rate）, CRP （C-reactive protein）, and RF （rheumatoid factor）. Serum levels of iron and TIBC （total iron binding capacity） were measured spectrophotometrically, while TS% （transferrin saturation percentage） and transferrin concentration were calculated mathematically. Serum concentrations of IL-6 （interleukin-6） and ferritin were measured using an ELISA （enzyme-linked immunosorbent assay）. The results of serum concentration of IL-6 （interleukin-6） and ferritin were significantly elevated （P 〈 0.0001） in patients with RA compared to those of healthy controls. On the other hand, serum concentrations of iron, TIBC （total iron binding capacity）, TS% （transferrin saturation percentage） and transferrin concentration were significantly decreased in patients with RA compared with those of healthy controls. These findings suggest that anemia is the most frequent observations in patients with RA and mostly associative with increasing level of interleukin-6.

Correlation of interleukin-6572C/G gene polymorphism with airway inflammation and remodeling in patients with COPD

Objective:To study the correlation of interleukin-6 (IL-6) 572C/G gene polymorphism with airway inflammation and remodeling in patients with COPD.Methods: Patients with stable COPD who were treated in Hanzhong Central Hospital between March 2015 and December 2017 were selected and enrolled in the COPD group of the study, and healthy volunteers who received physical examination in Hanzhong Central Hospital during the same period and had general information matched with that of patients with COPD were selected as the control group. The peripheral blood was collected to detect the IL-6 gene 572 C/G locus polymorphism, and the serum was collected to detect the levels of inflammatory response mediators and airway remodeling indexes.Results:The proportion of GG genotype in COPD group was higher than that in control group, and the proportion of GC+CC genotype was lower than that in control group;serum IL-6, IL-21, IFN-γ, CXCL13, CTRP4, CTRP5, TGF-β1, VEGF, MMP2 and NE levels of COPD group were significantly higher than those of control group whereas 1-AT and TIMP1 levels were significantly lower than those of control group, and serum IL-6, IL-21, IFN-γ, CXCL13, CTRP4, CTRP5, TGF-β1, VEGF, MMP2 and NE levels of COPD patients with GG genotype were higher than those of COPD patients with GC+CC genotype whereas 1-AT and TIMP1 levels were lower than those of COPD patients with GC+CC genotype.Conclusion:The mutation from IL-6 gene 572C/G locus allele C to G can aggravate the inflammatory response and airway remodeling in the course of COPD.

Impact of interleukin 6 levels on acute lung injury risk and disease severity in critically ill sepsis patients

BACKGROUND Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury(ALI)and multiple organ dysfunction syndrome(MODS).Interleukin 6(IL-6)is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications.AIM To investigate the relationship among plasma IL-6 levels,risk of ALI,and disease severity in critically ill patients with sepsis.METHODS This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022.A total of 83 septic patients were enrolled.Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay.The development of ALI and MODS was monitored during hospitalization.Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II(APACHE II)and Sequential Organ Failure Assessment(SOFA)scores.RESULTS Among the 83 patients with sepsis,38(45.8%)developed ALI and 29(34.9%)developed MODS.Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI(median:125.6 pg/mL vs 48.3 pg/mL;P<0.001).Similarly,patients with MODS had higher IL-6 levels than those without MODS(median:142.9 pg/mL vs 58.7 pg/mL;P<0.001).Plasma IL-6 levels were strongly and positively correlated with APACHE II(r=0.72;P<0.001)and SOFA scores(r=0.68;P<0.001).CONCLUSIONElevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI andMODS.Higher IL-6 levels were correlated with greater disease severity,as reflected by higher APACHE II andSOFA scores.These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI anddisease severity in patients with sepsis.

Effect of Xuezhikang Capsule(血脂康胶囊)on Serum Tumor Necrosis Factor-αand Interleukin-6 in Patients with Nonalcoholic Fatty Liver Disease and Hyperlipidemia

Objective：To evaluate the effect of Xuezhikang Capsule（血脂康胶囊） on the serum levels of inflammatory factors such as tumor necrosis factor-α（TNF-α） and interleukin-6（IL-6） in patients with nonalcoholic fatty liver disease（NAFLD） and hyperlipidemia,and to explore whether it has anti-inflammatory effect.Methods：A total of 84 patients were randomly assigned to two groups with stratified block randomization, the treatment group（42 cases） and the control group（42 cases）.They were treated with Xuezhikang Capsule and polyene phosphatidylcholine capsule for twenty-four weeks,respectively.The changes in serum TNF-αand IL-6 were measured by enzyme linked immunosorbent assay before treatment and at the 12th and 24th week. Results：Compared with those before treatment,the serum levels of TNF-αand IL-6 significantly decreased in both groups after treatment（P〈0.01）.There was no significant change between the two groups for the treatments at different time points（P〉0.05） and between the two groups for treatments at the same time points （P〉0.05）.Conclusion：Xuezhikang Capsule can inhibit the serum inflammatory factor in patients with NAFLD and hyperlipidemia.

High levels of interleukin-6 and 8-iso-prostaglandin in the exhaled breath condensate and serum of patients with chronic obstructive pulmonary disease related pulmonary hypertension

Background Pulmonary hypertension （PH） is a common complication of chronic obstructive pulmonary disease （COPD）. Although alveolar hypoxia is considered as a main cause of PH in COPD, structural and functional changes of pulmonary circulation are apparent at the initial stage of COPD. We hypothesized that an inflammatory response and oxidative stress might contribute to the formation of PH in COPD. Methods We measured the levels of interleukin-6 （IL-6） and 8-iso-prostaglandin （8-iso-PSG） in exhaled breath condensate （EBC） and serum in 40 patients with COPD only or in 45 patients with COPD combined with PH. Pulmonary arterial systolic pressure （PASP） was assessed by Doppler echocardiography and defined as PH when the value of systolic pressure was greater than 40 mmHg. Results Compared with the COPD only group, the level of IL-6 in EBC was significantly increased in all 45 patients with COPD combined with PH （（8.27±2.14） ng/L vs. （4.95±1.19） ng/L, P 〈0.01）. The level of IL-6 in serum was also elevated in patients with COPD combined with PH compared with the COPD only group （（72.8±21.6） ng/L vs. （43.58±13.38） ng/L, P 〈0.01 ）. Similarly, we also observed a significant increase in the level of 8-iso-PSG in both EBC and serum in the COPD with PH group, compared with the COPD only group （EBC： （9.00±2.49） ng/L vs. （5.96±2.31） ng/L, P 〈0.01 and serum： （41.87±9.75） ng/L vs. （27.79±11.09） ng/L, P 〈0.01）. Additionally, the value of PASP in the PH group was confirmed to be positively correlated with the increase in the levels of IL-6 and 8-iso-PSG in both EBC and serum （r=0.477-0.589, P 〈0.05）. Conclusion The increase in the levels of IL-6 and 8-iso-PSG in EBC and serum correlates with the pathogenesis of PH in COPD.

Effects of Liandou Qingmai Recipe(连豆清脉方) on Endothelin-1,Nitric Oxide,Interleukin-6 and Interleukin-10 Levels in Patients with Coronary Heart Disease

Objective:To observe effects of Liandou Qingmai Recipe(连豆清脉方) on endothelin-1(ET-1),nitric oxide(NO),interleukin-6(IL-6) and IL-10 levels in patients with coronary heart disease.Methods:Total 101 cases with coronary heart disease were randomly divided into a treatment group(n=45) treated by Liandou Qingmai Recipe and a standard treatment group(control group,n=56),with a normal group of 16 health persons set up.Changes of ET-1,NO,IL-6 and IL-10 levels were measured before treatment and after treatment for two weeks.And the data were analyzed by SPSS 16.0 statistic software.Results:Before treatment,the levels of ET-1,IL-6 and IL-10 levels were significantly higher and NO was significantly lower in the patients with coronary heart disease than those in the normal group(90.7±12.7 ng/L vs 41.8±13.5 ng/L,9.17±0.18 ng/L vs 1.10±0.08 ng/L,1.94±0.26 ng/L vs 1.09±0.06 ng/L,and 92.2±17.7 μmol/L vs 124.5±27.2 μmol/L;all P<0.05),with no significant differences in the levels of ET-1,NO,IL-6 and IL-10 between the treatment group and the control group(P>0.05);After treatment,ET-1 and IL-6 significantly decreased in the treatment group and the control group,and NO increased in the treatment group;And IL-6 level was significantly lower and NO level was higher in the treatment group than those in the control group(4.48±1.22 ng/L vs 5.13±1.85 ng/L,117.4±22.3 μmol/L vs 92.4±17.1 μmol/L;both P<0.05);There was a positive correlation between IL-6 and IL-10,and a negative correlation between NO and IL-10(r=0.142,r=-0.152;both P<0.05).Conclusion:Liandou Qingmai Recipe can decline IL-6,IL-10 and ET-1 levels,and raise NO level in patients with coronary heart disease on the basis of standard treatment,so as to inhibit endothelial inflammatory response,improve vascular endothelial function,with stronger anti-AS action;And vascular endothelial lesion is related with inflammatory response.

Differential Roles of Interleukin-6 in Severe Acute Respiratory Syndrome-Coronavirus-2 Infection and Cardiometabolic Diseases

Severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)infection can lead to a cytokine storm,unleashed in part by pyroptosis of virus-infected macrophages and monocytes.Interleukin-6(IL-6)has emerged as a key participant in this ominous complication of coronavirus disease 2019(COVID-19).IL-6 antagonists have improved outcomes in patients with COVID-19 in some,but not all,studies.IL-6 signaling involves at least 3 distinct pathways,including classic-signaling,trans-signaling,and trans-presentation depending on the localization of IL-6 receptor and its binding partner glycoprotein gp130.IL-6 has become a therapeutic target in COVID-19,cardiovascular diseases,and other inflammatory conditions.However,the efficacy of inhibition of IL-6 signaling in metabolic diseases,such as obesity and diabetes,may depend in part on cell type-dependent actions of IL-6 in controlling lipid metabolism,glucose uptake,and insulin sensitivity owing to complexities that remain to be elucidated.The present review sought to summarize and discuss the current understanding of how and whether targeting IL-6 signaling ameliorates outcomes following SARS-CoV-2 infection and associated clinical complications,focusing predominantly on metabolic and cardiovascular diseases.

Interleukin-6 in bronchoalveolar lavage fluid from patients with COPD

Objective To obtain new insights into the behavior of Interleukin-6(IL-6)in bronchoalveolar lavage fluid (BALF)and released from alveolar macrophages(AM)in chronic obstructive pulmonary diseases (COPD),and reveal the relationship between IL-6 and the development of emphysema in COPD.Methods IL-6 in BALF and released by AM in BALF were examined in 7 non-smoking subjects and 21 patients with COPD.According to the 95% confidence limits of IL-6 in BALF from non-smoking subjects,the patients were divided into two groups:those who were within the limits were assigned to the first group,and those who were above the limits were assigned to the second group.Results The concentration of IL-6 released by AM was much higher in the second group than in the first one.Between the two groups,significant differences were found in pulmonary function.Conclusion Our results suggest that the concentration of IL-6 released by AM may be related with pulmonary function,and IL-6 may play a role in the development of emphysema in patients with COPD.

Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The &#x0201c;two-hit&#x0201c; hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-&#x003b1;, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.

Relationship between coronary atherosclerosis plaque characteristics and high sensitivity C-reactive proteins, interleukin-6

Background The relationship between inflammatory markers and the characteristics of coronary atherosclerosis plaques is uncertain. The aim of the present study was to evaluate the relationship between the characteristics of coronary atherosclerosis plaques and inflammatory markers such as high sensitivity C-reactive proteins （Hs-CRP） and interleukin-6 （IL-6）. Methods All patients suspected of having coronary heart disease （CHD） underwent Siemens 64-slice CT angiography （64-SCTA） to distinguish the quality of plaque of coronary artery lesions. Blood samples were taken to measure levels of serum Hs-CRP and IL-6 in different plaque groups and the control group and compared with the value of 64-SCTA for detection of coronary artery plaque. Results The sensitivity of detecting coronary artery plaque by 64-SCTA was 87.4%, the specificity was 87.1%, the positive predictive value was 82.2%, and the negative predictive value was 91.0%. Comparing the levels of serum Hs-CRP and IL-6 among plaque groups, the mean levels of serum Hs-CRP and IL-6 in three plaque groups were significantly higher than those in the control group （P 〈0.01）. The mean levels of serum Hs-CRP and IL-6 in the soft plaque group and mixed plaque group were significantly higher than those in hard plaque group （P〈0.01）. Plaque burden in the soft plaque group and mixed plaque group was significantly higher than in the hard plaque group （P 〈0.01）, but there was no statistical difference between the soft plaque group and mixed plaque group （P=-0.246）. There was a negative correlation between the CT scale and Hs-CRP and IL-6 levels in the soft plaque group （r= -0.621, P〈0.01, and r= -0.593, P 〈0.01 respectively）. There was a positive correlation between the plaque burden and Hs-CRP and IL-6 levels in the soft plaque group （r=0.579, P〈0.05 and r=0.429, P〈0.05 respectively）. Conclusions 64-SCTA is an effective way to distinguish the different quality of coronary atherosclerosis plaque. Serum Hs-CRP and IL-6 levels can be considered as the indexes to judge the degree of CHD and may reflect the activity of plaque in CHD patients. Thus it is important for clinical diagnosis and risk evaluation of acute coronary syndrome （ACS） patients.

A new in ammation marker of chronic obstructive pulmonary disease– adiponectin

BACKGROUND： This study was undertaken to measure the concentration of adiponectin （APN） in serum and induced sputum in patients with chronic obstructive pulmonary disease （COPD during acute exacerbation （AECOPD） and at stable stage and to determine the role of APN as a marker of in？ ammation in the pathogenesis of COPD.METHODS： All the patients in this prospective study were enrolled from October 2008 to October 2009, including 30 male AECOPD patients from the emergency department, 30 male stable COPD patients from the department of respiratory diseases, and 30 healthy non-smoking male controls from the department of medical examination. The serum and induced sputum were collected from each patient. All of the patients had normal weight （BMI range 18.5-24.9 kg/m2）. Patients with severe bronchial asthma, bronchiectasis or autoimmune disease were excluded. Cell count and classi？ cation was performed for the induced sputum. The concentrations of APN, IL-8, IL-6 and TNF-α were measured by ELISA. Pulmonary function was tested among the three groups. Comparisons between the groups were conducted by Student＇s t test, ANOVA analysis or nonparametric test. Correlation analysis was carried out by Pearson＇s product-moment correlation coef？ cient test or Spearman＇s rank-order correlation coef？ cient test.RESULTS： The concentrations of APN in the serum or induced sputum in AECOPD patients were signi？ cantly higher than those in stable COPD patients or healthy non-smoking controls （P〈0.01）. The concentration of APN in stable COPD patients was signi？ cantly higher than that in healthy non-smoking controls （P〈0.01）. For the AECOPD patients, APN was positively correlated with IL-8 and TNF-α in the serum and induced sputum （r=0.739, 0.734, 0.852, 0.857 respectively, P〈0.05）. For the stable COPD patients, APN was also positively correlated with IL-8 and TNF-α in the serum and induced sputum （r=0.751, 0.659, 0.707, 0.867 respectively, P〈0.05）. In addition, for the AECOPD patients, APN was positively correlated with the percentage of neutrophils in the induced sputum （r=0.439, P〈0.05）.CONCLUSIONS： APN is involved in the process of systematic and airway inflammation ofCOPD. This process is related to neutrophils in the airway, IL-8 and TNF-α. APN could be used as a new marker for in？ ammation of COPD.

Mitogen-activated protein kinase-activated protein kinase 2 regulates tumor necrosis factor-induced interleukin-6 expression via human antigen R

Background Human antigen R （HuR） is a ubiquitously expressed member of the ELAV family, and has relatively high cytoplasmic abundance in lung tissue regenerating after injury. In this study, we investigated whether mitogen-activated protein kinase （MAPK）-activated protein kinase 2 （MK2） and HuR participate in the tumor necrosis factor （TNF）-induced expression of interleukin-6 （IL-6）. Methods Human pulmonary microvascular endothelial cells were treated with TNF following short interfering RNAmediated knockdown of MK2 or HuR. Cell supernatants were collected to detect the mRNA and protein expression of IL-6 at different time points, The expression and half-life of IL-6 mRNA were then determined in cells that had been treated with actinomycin D. Finally, after knockdown of MK2, the cytoplasmic expression of HuR protein was analyzed using Western blotting. Results MK2 or HuR knockdown decreased both the mRNA and protein expression of IL-6 in TNF-stimulated cells. In MK2 knockdown cells, the half-life of IL-6 mRNA was reduced to 36 minutes, compared with 67 minutes in the control group. In HuR knockdown cells, the half-life of IL-6 mRNA decreased from 62 minutes to 24 minutes. Further analysis revealed that knockdown of MK2 resulted in reduced HuR protein expression in the cytoplasm. Conclusions MK2 regulates the TNF-induced expression of IL-6 by influencing the cytoplasmic levels of HuR.

Comparative analysis of Nε-carboxymethyl-lysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients

BACKGROUND Coronary artery disease(CAD)is a major cause of death worldwide,and India contributes to about one-fifth of total CAD deaths.The development of CAD has been linked to the accumulation of Nε-carboxymethyl-lysine(CML)in heart muscle,which correlates with fibrosis.AIM To assess the impact of CML and inflammatory markers on the biochemical and cardiovascular characteristics of CAD patients with and without diabetes.METHODS We enrolled 200 consecutive CAD patients who were undergoing coronary angiography and categorized them into two groups based on their serum glycosylated hemoglobin(HbA1c)levels(group I:HbA1c≥6.5;group II:HbA1c<6.5).We analyzed the levels of lipoproteins,plasma HbA1c levels,CML,interleukin-6(IL-6),tumor necrosis factor alpha(TNF-α),and nitric oxide.RESULTS Group I (81 males and 19 females) patients had a mean age of 54.2 ± 10.2 years, with a mean diabetes duration of4.9 ± 2.2 years. Group II (89 males and 11 females) patients had a mean age of 53.2 ± 10.3 years. Group I had moresevere CAD, with a higher percentage of patients with single vessel disease and greater stenosis severity in the leftanterior descending coronary artery compared to group II. Group I also exhibited a larger left atrium diameter.Group I patients exhibited significantly higher levels of CML, TNF-α, and IL-6 and lower levels of nitric oxide ascompared with group II patients. Additionally, CML showed a significant positive correlation with IL-6 (r = 0.596,P = 0.001) and TNF-α (r = 0.337, P = 0.001) and a negative correlation with nitric oxide (r=-4.16, P = 0.001). Oddsratio analysis revealed that patients with CML in the third quartile (264.43-364.31 ng/mL) were significantlyassociated with diabetic CAD at unadjusted and adjusted levels with covariates.

血清KL-6水平对类风湿关节炎合并间质性肺病的预测及其与预后的关系

目的:探讨血清KL-6水平对类风湿关节炎(RA)合并间质性肺病(RA-ILD)的预测及其与预后的关系。方法:选取2018年1月至2021年1月内蒙古医科大学附属医院收治的RA患者70例,依据其是否合并间质性肺病(ILD)分为RA-ILD组(34例)和RA组(36例),对两组患者的临床资料进行单因素分析,重点比较两组患者血清中KL-6表达水平及实验室指标、肺功能、影像学等相关性分析,多因素Logistic回归分析影响RA-ILD的危险因素。结果:两组患者性别、吸烟史、年龄及发病年龄、病程、DAS28、KL-6、WBC、UA、RF、抗CCP抗体、TLC%Pred、DLCO%Pred差异有统计学意义(P<0.05);RA-ILD组患者临床症状占比关节痛较为突出,HRCT表现胸膜粘连增厚较为突出;Spearson相关性分析显示,RA-ILD组患者血清KL-6水平与TLC%Pred、VC%Pred、DLCO%Pred呈显著负相关(P<0.05),与RF、抗CCP抗体水平呈显著正相关(P<0.05);与FEV1%Pred、FEV1/FVC无明显相关性(P>0.05);RA-ILD组患者治疗前KL-6表达水平显著高于RA组,治疗后差异无统计学意义(P>0.05);随访1年,RA-ILD组有6例患者死亡,经分析死亡组KL-6表达水平显著高于未死亡组(P<0.05);高龄、男性、吸烟、抗CCP抗体升高及KL-6升高是影响RA-ILD的独立危险因素(P均<0.05);血清KL-6预测ROC曲线下最大面积为0.802,95%置信区间为0.743~0.866,灵敏度、特异度分别为0.853、0.827,联合检测ROC曲线下最大面积为0.854,表明该模型预测能力较强。结论:RA-ILD组患者血清KL-6水平显著升高,KL-6可作为早期发现ILD的血清学指标,联合肺功能检测可更早发现ILD,早期诊断对于治疗及预后有重要意义。

The Effect of Chloroquine on Pro-Inflammatory Cytokines Levels in Graves’ Disease: Historical Cohort from a Pilot Randomized Controlled Trial

Objectives: Analyzing the trend in the serum inflammatory cytokines levels in a historical cohort of patients treated with combination of chloroquine and methimazole. Material and methods: We analyzed the pro-inflammatory serum cytokines level [Interleukin-6(IL-6), Tumor Necrosis Factor alpha (TNF-α), Interleukin 1 alpha (IL-1 α) and Interferon gamma (INF-γ)] in the stored blood samples of 22 patients with Graves’ disease who previously randomized to receive either chloroquine and methimazole combination therapy or methimazole monotherapy. Total T3, T4 and TSH levels were measured by an enzyme linked immunosorbent assay (ELISA) method (DRG, New York, USA) and the result was published previously. In this study we used an ELISA method (Bender Medsystem Vienna Austria) to measure serum pro-inflammatory cytokines in the first 6 months of trial. Results: No significant differences in serum cytokines concentration were observed between the two treatment groups (p > 0.05). Although it was not statistically significant, serum INF-gamma concentration tended to be lower in the chloroquine group after four months of therapy (p = 0.12). Conclusion: In this study we found changes in the serum thyroid hormones level did not accompany concomitant changes in the serum cytokines levels in two treatment groups. Therefore it is possible that chloroquine reduce serum thyroid hormones levels independent of its immunomodulatory effect.