Effect of flurbiprofen combined with prednisolone on interleukin-6 in elderly surgery patients

Objective: To determine the effect of flurbiprofen combined with prednisolone on interleukin-6 in elderly surgery patients. Methods: In this double-blind randomized controlled study, patients aged 65 to 80 who were undergoing spinal fusion surgery for disc herniation were administered flurbiprofen 100 mg (P group, flurbiprofen group), prednisolone 0.6 mg/kg (D group, prednisolone group), prednisolone 0.6 mg/kg plus flurbiprofen 100 mg (P + D group, flurbiprofen + prednisolone group) or normal saline (S group, saline group) 15 minutes before the induction of anesthesia. Plasma samples were collected before surgery (T0) and on day 1 (T1), day 2 (T2) and day 3 (T3) following surgery. At the same time, systemic inflammatory response syndrome (SIRS) was assessed by SIRS criteria. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) for collected samples were measured. Results: Other groups had significantly lower levels of IL-6, CRP and occurrence of SIRS than S group (p < 0.05). Compared to groups P and D, the levels of IL-6 and CRP in P + D group were significantly lower on T1 (p < 0.05). Peak levels of IL-6 in all groups were presented on T1 (p 0.05). The levels of CRP within three days were significantly different but did not show peak levels (p > 0.05). Conclusion: Compared to prednisolone or flurbiprofen, combining flurbiprofen with prednisolone in elderly surgery patients led to an increased suppression of IL-6.

6-Gingerol, asarinin, and deoxyschizandrin improve bronchial epithelium functions in an interleukin-13einduced BEAS-2B cell model

Objective:To explore the effects of 6-gingerol,asarinin,and deoxyschizandrindthe main components of Zingiber officinale(Willd.)Rosc.(Gan Jiang),Asarum heterotropoides f.var.mandshuricum(Maxim.)(Xi Xin),and Schisandra chinensis(Turcz.)Baill.(Wu Wei Zi),respectivelydon an interleukin(IL)-13einduced BEAS-2B cell model in vitro.Methods:The BEAS-2B cell model was established using 25 ng/mL IL-13 combined with 1%fetal bovine serum(FBS)in vitro.Mitoquinone mesylate(Mito-Q)treatment was used as a positive control group,and different concentrations of 6-gingerol,asarinin,and deoxyschizandrin were used to treat the models.The level of reactive oxygen species(ROS)production was detected by flow cytometry.The expression levels of LC3B,Beclin1,adenosine 50-monophosphate(AMP)eactivated protein kinase(AMPK),phosphory-lated-AMPeactivated protein kinase(P-AMPK),dynamin-related protein 1(DRP1),and mitochondrial fusion protein 2(MFN2)were detected by Western blot.Mitochondrial membrane potential(MMP)assay kit with JC-1 was utilized to detect the level of MMP.Results:The BEAS-2B cells exposed to 25 ng/mL IL-13 with 1%FBS showed an increased ROS level and a decreased MMP.6-Gingerol,asarinin,and deoxyschizandrin were able to downregulate ROS level and upregulate the MMP in the BEAS-2B model.Asarinin and deoxyschizandrin reduced the expression of autophagy protein LC3B,while deoxyschizandrin significantly increased the expression of DRP1 in the BEAS-2B model.Conclusion:6-Gingerol,asarinin,and deoxyschizandrin can reduce ROS generation and increase MMP,but have different regulatory effects on the expression of autophagy protein and mitochondrial mitotic protein.The three components have both synergistic and complementary effects in classic medicine compatibility.This study may provide an innovative strategy to reduce the lung inflammation related to IL-13.

Clinical analysis between serum 25-hydroxyvitamin D3, interleukin-6 levels and febrile convulsion in children

Objective:To investigate the relation between febrile convulsions and 25hydroxy-vitamin D_(3)[25-(OH)D_(3)]and interleukin-6(IL-6)levels in children.Methods:241 children(divided into simple febrile convulsions and complex febrile convulsions),who were diagnosed with febrile convulsions at the Women and Children's Medical Center of Hainan Province from January 2017 to October 2022,were selected into the febrile convulsions group;100 healthy children,who had no uncomfortable symptoms and attended the outpatient clinic of the Women and Children's Medical Center of Hainan Province for physical examination,for the control group.All the subjects measured the serum 25-(OH)D_(3) and IL-6 levels,and clinical information,such as age,gender and season,was recorded.Results:1)Serum 25-(OH)D_(3) levels in the febrile convulsion group were significantly lower than in the healthy control group(78.77±20.37 nmol/L versus 96.55±29.74 nmol/L,respectively),and there was a statistically significant between the two groups(t value-6.359,P<0.001).Serum IL-6 levels in the febrile convulsion group were significantly higher than in the healthy control group,and there was a statistically significant between the two groups(Z value of-14.291,P<0.001).2)Serum 25-(OH)D_(3) levels in children with complex febrile convulsions were significantly lower than those in children with simple febrile convulsions,and the difference between the two groups was statistically significant(t-value of 6.612,P<0.05).IL-6 levels were higher in children with complex febrile convulsions than in children with simple febrile convulsions,and the difference between the two groups was statistically significant(Z value-10.151,P<0.001).The difference in the severity of febrile convulsions was statistically significant in serum 25-(OH)D_(3) levels(x^(2)=29.83,P<0.001).3)The results of correlation analysis showed that serum 25-(OH)D_(3) level was negatively correlated with febrile convulsion(γ=-0.393,P<0.05);serum 25-(OH)D_(3) level was positively correlated with that(γs=0.328,P<0.05).4)The correlation analysis results showed that the serum 25-(OH)D_(3) level was negatively correlated with the clinical characteristics of febrile convulsion(γ=-0.393,P<0.05).However,serum IL-6 water is positively correlated with it(γs=0.328,P<0.05).4)In contrast,there was no statistically significant difference in serum 25-(OH)D_(3) levels among children with febrile convulsions in different seasons(P>0.05).Conclusions:There is a correlation between febrile convulsion and serum levels of 25-(OH)D_(3) and IL-6.25-(OH)D_(3) and IL-6 may participate in the pathogenesis of febrile convulsion.

Association between Metabolic Syndrome Components and Serum High-Sensitivity C-Reactive Protein or Interleukin-6 Levels among Congolese Adults

Metabolic syndrome (MetS) and its components have been linked to elevated serum levels of inflammatory biomarkers such as C-reactive protein, interleukin-6, interleukin-1β and tumor necrosis factor alpha. The aim of our study was to address the association between MetS components with serum hs-CRP and IL-6 levels among Congolese adults. A total of 357 participants (aged 30 - 87 years) were included in this cross-sectional study. Anthropometrics were collected and fasting blood sampled for assessment of fasting blood glycaemia (FBG), lipids and inflammatory parameters using commercially available assays. NCEP-ATPIII criteria were used to define MetS. The Median (IQR) hs-CRP and IL-6 levels were higher in participants with MetS than in those without ([7 (4, 14) versus 6 (4, 8)] mg/L;p = 0.092 and [23.8 (20.9, 27.6) versus 22.3 (19.5, 25.0)] pg/mL;p = 0.002). hs-CRP and IL-6 levels were significantly higher in females with MetS than in those without, but not in males. Among participants, only TG was correlated with hs-CRP (r = 0.149, p = 0.007), and a significant correlation was observed between TG (r = 0.116, p = 0.037), FBG (r = 0.208, p = 0.000), HDL-C (r = −0.119, p = 0.034) and SBP (r = 0.143, p = 0.010) and IL-6. In males, hs-CRP levels were positively correlated with TG (0.316;p = 0.000), negatively with HDL-C (r = −0.290, p = 0.0022), without such correlations in females. In Ames, IL-6 levels were positively correlated with FBG (r = 0.202;p = 0.035), and negatively with HDL-C (r = −0.249, p = 0.009). Significant correlations between IL-6 levels and FBG (r = 0.214;p = 0.000) or SBP (r = 0.227, p = 0.000) were observed in females. Logistic regression analysis was carried out to identify the relationship between MetS components and hs-CRP or IL-6. Values of area under receiver-operating characteristic (ROC) curves suggest potential use of serum hs-CRP (AUC = 0.675) and IL-6 (AUC = 0.656) as diagnostic biomarkers of MetS. Combination of hs-CRP and IL-6 improved diagnosis accuracy, yielding a 0.698 ROC curve area. MetS components are associated with hs-CRP and IL-6 levels among adults Congolese. Combining the two biomarkers hs-CRP and IL-6 improves Mets diagnostic accuracy compared to hs-CRP or IL-6 alone.

Mechanism of Yanghe Pingchaun granules on airway remodeling in asthmatic rats based on IL-6/JAK2/STAT3 signaling axis

Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.

联合检测GR、NO、IL-6对儿童病毒性心肌炎的评价

目的联合几项免疫介导的血清学指标来提高对儿童儿童病毒性心肌炎(VMC)的诊断效率,为临床提供早期的诊断价值,避免漏检对患儿引起的不良结局。方法收集泗洪医院2018年1月至2022年6月在儿科住院就诊符合条件的45例VMC病例纳入VMC组,45例单纯病毒感染患儿纳入NVMC组以及体检的50名正常儿童纳入对照组。收集研究对象一般资料,包括白细胞介素6(IL-6)、谷胱甘肽还原酶(GR)、一氧化氮(NO)以及心肌酶谱、肌钙蛋白结果。用受试者工作特征(ROC)曲线各单项指标对VMC的价值分析,并采用Logistic回归模型构建模型来预判VMC。结果VMC组的肌酸激酶同工酶(CK-MB)、天门冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)、肌钙蛋白I(cTnI)、NO、IL-6含量明显高于NVMC组和对照组,而GR含量则明显低于后两组;用各单项指标来对VMC进行ROC曲线分析,结果显示特异性最高的是cTnI的0.907,敏感性最高的是IL-6的0.912,AUC面积最大的是NO,为0.883;由cTnI、CK-MB、GR、NO、IL-6等5项指标联合建立的回归模型,当诊断界值定为0.55时,模型对VMC的AUC为0.976,敏感性为0.977,特异性为0.982,此时约登指数最大为0.959。结论用NO、GR、IL-6联合cTnI、CK-MB构建的回归模型对VMC的诊断特异性以及敏感性明显高于其他的单一指标。能够为临床医生及早的诊断儿童VMC提供有力的依据和辅助。

Plasma levels of tumor necrotic factor-alpha and interleukin-6, -8 during orthotopic liver transplantation and their relations to postoperative pulmonary complications

BACKGROUND: Pulmonary complications after orthoto- pic liver transplantation (OLT) include high morbidity and mortality. Experimental data have suggested hepatic ische- mia and reperfusion are induced by pro-inflammatory cyto- kines. The high level of inflammatory cytokines might ad- ditionally influence pulmonary cappillary fluid filtration. The objectives of this study were to measure the concentra- tions of tumor necrotic factor-alpha (TNF-α), interleukin- 6 (IL-6) and interleukin-8 (IL-8) during OLT and to in- vestigate the relationship between these cytokines and post- operative pulmonary complications. METHODS: Twenty-two patients undergoing OLT were divided into two groups according to whether they had postoperative pulmonary complications: group A consis- ting of 8 patients with postoperative pulmonary complica- tions , and group B consisting of 14 patients without post- operative pulmonary complications. Enzyme-linked im- munoassay (ELISA) was used to determine serum TNF-α, IL-6 and IL-8. Blood samples were taken at the beginning of operation (T0 ), clamping and cross-clamping of the in- ferior cava and portal vein (T1, T2 ), 90 minutes and 3 hours after reperfusion (T3 , T4 ) and 24 hours after opera- tion (T5). RESULTS: The level of PaO2/FiO2 in group A was lower than that in group B ( P <0. 05 ). The concentrations of TNF-α, IL-6 and IL-8 in the two groups increased rapidly at T2 , peaked at T3 , decreased rapidly after T3 until 24 hours after operation. The concentrations of TNF-α, IL-6 and IL-8 in group A were higher than those in group B at T2, T3, and T4(P<0.05). CONCLUSION: After un-clamping of the inferior cava and portal vein, the serum concentrations of TNF-α, IL-6 and IL-8 increased may be related to pulmonary injury after he- patic ischemic reperfusion.

Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma

Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5' and 3' flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the data in the literature on the genetic association between the -174 G/C polymorphism and some specific liver diseases characterized by different etiologies are still controversial. In particular, most of the studies are quite unanimous in describing a correlation between the presence of the high-producer genotype and a worse evolution of the chronic liver disease. This is valid for patients with hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis and hepatocellu-lar carcinoma (HCC) whatever the etiology. Studies in hepatitis B virus-related chronic liver diseases are not conclusive, while specific populations like non alcoholic fatty liver disease/non-alcoholic steatohepatitis, autoimmune and human immunodeficiency virus/HCV coinfected patients show a higher prevalence of the lowproducer genotype, probably due to the complexity of these clinical pictures. In this direction, a systematic revision of these data should shed more light on the role of this polymorphism in chronic liver diseases and HCC.

Tumor necrosis factor-α and interleukin-6 in cirrhotic patients with spontaneous bacterial peritonitis

AIM:To evaluate the role of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in cirrhotic patients who have hepatic and renal impairment with spontaneous bacterial peritonitis(SBP).METHODS:We prospectively studied 120 cirrhotic patients with SBP and 80 cirrhotic patients with sterile ascitic fluid.They included 144 males and 56 females with ages ranging between 34 and 62 years.The diagnosis of cirrhosis was established by clinical and laboratory criteria that did not require histological confirmation.The severity of underlying liver disease was evaluated using Pugh's modification of Child's criteria(Child-Pugh scores).Ascitic fluid was sent to the laboratory for cell count,culture,sensitivity testing,and measurement of chemical elements(i.e.,albumin,glucose).Specimens were inoculated into aerobic and anaerobic blood culture bottles.Serum and ascitic fluid were also collected in sterile tubes at study entry(before the initiation of antibiotic treatment) and 48 h later.Assays for TNF-α and IL-6 in the serum and ascitic fluid were performed with an immunoenzymometric assay using manufacture's instructions.RESULTS:Cytokine levels in serum and ascitic fluid were significantly higher in the patients with SBP.(plasma TNF-α:135.35 ng/mL ± 11.21 ng/mL vs 92.86 ng/mL ± 17.56 ng/mL,P < 0.001;plasma IL-6:32.30 pg/mL ± 7.07 pg/mL vs 12.11 pg/mL ± 6.53 pg/mL,P < 0.001;ascitic fluid TNF-α:647.54 ± 107.11 ng/mL vs 238.43 ng/mL ± 65.42 ng/mL,P < 0.001);ascitic fluid IL-6:132.84 ng/mL ± 34.13 vs 40.41 ± 12.85 pg/mL,P < 0.001).About 48(40%) cirrhotic patients with SBP developed renal and hepatic impairment and showed significantly higher plasma and ascitic fluid cytokine levels at diagnosis of infection.[(plasma TNF-α:176.58 ± 17.84 vs 135.35 ± 11.21 ng/mL)(P < 0.001) and(IL-6:57.83 ± 7.85 vs 32.30 ± 7.07 pg/mL)(P < 0.001);ascitic fluid TNF-α:958.39 ± 135.72 vs 647.54 ± 107.11 ng/mL,(P < 0.001),ascitic fluid IL-6:654.74 ± 97.43 vs 132.84 ± 34.13 pg/mL,(P < 0.001)].Twenty nine patients(60.4%) with SBP and renal impairment died whereas,only four patients(5.55%) with SBP but without renal impairment died from gastrointestinal hemorrhage(P < 0.0005).CONCLUSION:It appears that TNF-α production may enhance liver cell injury and lead to renal impairment.This correlated well with the poor prognosis and significantly increased mortality associated with SBP in cirrhotic patients.

Interleukin-6 and ratio of plasma interleukin-6/interleukin-10 as risk factors of symptomatic lumbar osteoarthritis

AIM To determine the role of cartilage oligomeric matrix protein(COMP), interleukin(IL)-6, IL-10 and ratio of IL-6/IL-10 as risk factors of symptomatic lumbar osteoarthritis(OA) in postmenopausal women with estrogen deficiency.METHODS Case-control study had been conducted in Sanglah General Hospital from October 2015 until March 2016. The blood samples were obtained and analyzed by enzyme-linked immunosorbent assay(ELISA).RESULTS From 44 pairs of samples which divided into 44 samples as case group and 44 samples as control group showed that high level of COMP in estrogen deficiency postmenopausal women were not at risk(OR = 0.7; 95%CI: 0.261-1.751; P = 0.393) for symptomatic lumbar OA(cut-off point 0.946). Estrogen deficiency in postmenopausal women with the high level of IL-6 had 2.7 times risk(OR = 2.7; 95%CI: 0.991-8.320; P = 0.033) for symptomatic lumbar OA from the low level of IL-6(cut-off point 2.264). At lower level of IL-10, there was no risk for symptomatic lumbar OA(OR = 0.6; 95%CI: 0.209-1.798; P = 0.345) than with the higher level of IL-10(cut-off point 6.049). While the high ratio of IL-6/IL-10 level in estrogen deficiency postmenopausal women gave 3.4 times risk(OR = 3.4; 95%CI: 1.204-11.787; P = 0.011)for symptomatic lumbar OA than the low ratio of IL-6/IL-10 level(cut-off point 0.364).CONCLUSION High ratio of IL-6/IL-10 plasma level was the highest risk factor for causing symptomatic lumbar OA in postmenopausal women with estrogen deficiency.

High levels of serum interleukin-6 increase mortality of hepatitis B virus-associated acute-on-chronic liver failure

BACKGROUND Patients with hepatitis B virus-associated acute-on-chronic liver failure(HBVACLF)present a complex and poor prognosis.Systemic inflammation plays an important role in its pathogenesis,and interleukin-6(IL-6)as a pro-inflammatory cytokine is related with severe liver impairment and also plays a role in promoting liver regeneration.Whether serum IL-6 influences HBV-ACLF prognosis has not been studied.AIM To determine the impact of serum IL-6 on outcome of patients with HBV-ACLF.METHODS We performed a retrospective study of 412 HBV-ACLF patients.The findings were analyzed with regard to mortality and the serum IL-6 level at baseline,as well as dynamic changes of serum IL-6 within 4 wk.RESULTS The serum IL-6 level was associated with mortality.Within 4 wk,deceased patients had significantly higher levels of IL-6 at baseline than surviving patients[17.9(7.3-57.6)vs 10.4(4.7-22.3),P=0.011].Patients with high IL-6 levels(>11.8 pg/mL)had a higher mortality within 4 wk than those with low IL-6 levels(≤11.8 pg/mL)(24.2%vs 13.2%,P=0.004).The odds ratios calculated using univariate and multivariate logistic regression were 2.10(95%confidence interval[CI]:1.26-3.51,P=0.005)and 2.11(95%CI:1.15-3.90,P=0.017),respectively.The mortality between weeks 5 and 8 in patients with high IL-6 levels at 4 wk was 15.0%,which was significantly higher than the 6.6%mortality rate in patients with low IL-6 levels at 4 wk(hazard ratio=2.39,95%CI:1.05-5.41,P=0.037).The mortality was 5.0%in patients with high IL-6 levels at baseline and low IL-6 levels at 4 wk,7.5%in patients with low IL-6 levels both at baseline and at 4 wk,11.5%in patients with low IL-6 levels at baseline and high IL-6 levels at 4 wk,and 16.7%in patients with high IL-6 levels both at baseline and at 4 wk.The increasing trend of the mortality rate with the dynamic changes of IL-6 was significant(P for trend=0.023).CONCLUSION A high level of serum IL-6 is an independent risk factor for mortality in patients with HBV-ACLF.Furthermore,a sustained high level or dynamic elevated level of serum IL-6 indicates a higher mortality.

Tumor growth inhibition effect of hIL-6 on colon cancer cells transfected with the target gene by retroviral vector

AIM To observe the tumor inhibitory effects bytransfecting IL-6 cDNA into colon cancer cell lineHT-29 with retroviral vector pZIP cDNA.METHODS Human IL-6 gene was reconstructedin retrovirus vector and transfected into incasingcells PA317 by lipofectamine mediated method,the clones of the cells transferred with hlL-6were selected by G418,and targeted HT-29 cellswere infected with the virus granules secretedfrom PA317 and also selected by G418.Test genetranscription and expression level byhybridization,ELISA and MTT assay,etc.Analyze tumor inhibitory effects according to thecell growth curve,plating forming rate andtumorigenicity in nude mice.RESULT Successfully constructed andtransfected recombinant expressing vectorspZIPIL-6 cDNA and got positive transfected celllines.The colon cancer cell line(HT-29 IL-5)transfected with the hlL-5 gene by retroviralvector was established.The log proliferationperiod and the doubling time of this cell line wasbetween 4 to 7 days and 2.5 days according tothe direct cell count,the cell proliferation wasobviously inhibited with MTT assay,the platinginhibitory rate was 50% by plating efficiencytest.When HT-29 IL-6 cells were inoculated intothe nude mice subcutaneously,carcinogenicactivity of the solid tumor was found superior tothe control group and the size of tumor was notsignificantly enlarged.Injection of combinationvirus fluid containing 11.-6 gene intotransplantation tumors could inhibit the growthand development of the tumor.CONCLUSION IL-6 could inhibit the growth andproliferation of colon cancer cells by retroviralvector-mediated transduction.

The Role of High-sensitivity C-reactive Protein, Interleukin-6 and Cystatin C in Ischemic Stroke Complicating Atrial Fibrillation

This study examined the role of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and cystatin C in ischemic stroke complicating atrial fibrillation (AF) and the relationship of systemic inflammation with this disease in order to identify AF patients who are at high risk of stroke and need optimal anticoagulant therapy.A total of 103 AF patients, simple (n=75) or complicated by ischemic stroke (n=28), and 112 control subjects were recruited.IL-6 level was detected by using enzyme linked immunosorbent assay.Cystatin C and hsCRP levels were measured by means of a particle-enhanced immunonephelometric assay.The results showed that the AF patients had higher levels of hsCRP (P=0.004), IL-6 (P=0.000), and cystatin C (P=0.000) than control subjects.Plasma hsCRP level was increased in the AF patients with ischemic stroke as compared to the patients with simple AF (P=0.036).The AF patients who had the level of hsCRP exceeding 3.83 mg/L were at a higher risk than those with hsCRP level lower than 3.83 mg/L (P=0.030).After adjusting for other factors, cystatin C remained positively associated with IL-6 (r=0.613) and hsCRP (r=0.488).It was concluded that hsCRP is positively correlated with ischemic stroke complicating AF and may be a risk factor independent of other risk factors for AF.Elevated cystatin C level is also indicative of the increased risk of AF.

Interleukin-1α, 6 regulate the secretion of vascular endothelial growth factor A, C in pancreatic cancer

Vascular endothelial growth factor (VEGF, namely VEGF-A) is an angiogenic polypeptide and VEGF-C is a lymphangiogenic polypeptide that has been implicated in cancer growth, invasion and metastasis. Several cytokines and growth factors play an important part in cancer progression. These cytokines and growth factors are the principal mediators of cancer cells-stromal cell interaction , which is critical for invasion of cancer cells to the surrounding tissues and metastatic dissemination to distant organs. In this study, we studied VEGF-A, C expression in cultured human pancreatic cancer cell lines and whether the presence of VEGF-A, C in the cell lines is regulated by cytokines interleukin-lct (EL-1α), and interleukin-6 (IL-6). METHODS: We used Northern blot and Western blot methods to analyze expression of the gene and protein of VEGF-A, C in all 6 tested cell lines (ASPC-1, CAPAN-1, MIA-PaCa-2, PANC-1, COLO-357 and T3M4) respectively. To analyze what is the regulator for this VEGF-A, C expression in pancreatic cancer,we used the reverse transcription -polymerase chain reaction (RT-PCR) method to analyze VEGF-A, C expression in cultured human pancreatic cancer cell lines (CAPAN-1 and COLO-357) under the stimulation with IL-1α (10μg/L) or IL-6 (100 μg/L). RESULTS:Northern blot analysis revealed the presence of the 4.1-kb VEGF-A mRNA transcript and 2.4-kb VEGF-C mRNA transcript in all 6 tested cell lines. Immunoblotting with highly specific anti-VEGF-A, anti-VEGF-C antibody revealed the presence of a molecular weight of 43-kDa VEGF-A protein and 55-kDa VEGF-C protein in all the cell lines. RT-PCR analysis revealed the levels of the VEGF-A and VEGF-C gene were 1-2 fold and a 1-fold increase in the COLO-357 cell line by stimulation with IL-la, however, no effect was found in the CAPAN-1 cell line. The levels of the VEGF-A and VEGF-C gene were 2-5 fold and a 1-fold increase in the CAPAN-1 cell line by stimulation with IL-6, but, no effect was found in the COLO-357 cell line. CONCLUSION:These findings suggested that the expression of VEGF-A, C and their regulation by IL-1α, IL-6 in pancreatic cancer contributes to the lymphatic and distant metastasis and the disease progression.

Clinicopathological significance of overexpression of interleukin-6 in colorectal cancer

AIM To compare the expression levels of interleukin(IL)-6 in colorectal cancer(CRC) tissues and adjacent noncancerous tissues, and analyse the correlation of IL-6 expression with the clinicopathological parameters of CRC. METHODS Fifty CRC tissue specimens and 50 matched adjacent mucosa specimens were collected. The expression of IL-6 in these clinical samples was examined by immunohistochemical staining. The correlation between IL-6 expression and clinicopathological parameters was assessed by statistical analysis.RESULTS IL-6 expression was significantly elevated in CRC tissues compared with noncancerous tissues(P < 0.001). IL-6 expression was positively correlated with tumour TNM stage(P < 0.001), but a negative correlation was detected between IL-6 expression and tumor histological differentiation in CRC(P < 0.05). Furthermore, IL-6 expression was associated with invasion depth and lymph node metastasis in CRC. CONCLUSION IL-6 might be a useful marker for predicting a poor prognosis in patients with CRC and might be used as a potential therapeutic target in CRC.

First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy

We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies(infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro-inflammatory cytokine interleukin-6(IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody(tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNF, IL-21 and IFN-γ. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may leadto aggravation of anti-TNF resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling.

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.

hs-CRP、IL-6和WBC检测对小儿呼吸道病毒感染的诊断价值

目的 探讨超敏C-反应蛋白(hs-CRP)、白细胞介素-6(IL-6)、白细胞(WBC)计数检测对小儿呼吸道病毒感染的诊断价值。方法 选取2020年9月至2022年2月收治的50例小儿呼吸道感染患儿为研究对象(病毒感染组),另选50例同期健康儿童为对照组。比较2组hs-CRP、IL-6、WBC水平及一般资料,分析小儿呼吸道病毒感染危险因素,并绘制ROC曲线。结果 病毒感染组患儿hs-CRP、IL-6、D-二聚体、降钙素原(PCT)、WBC、血清淀粉样蛋白(SAA)水平显著高于对照组(P<0.05);病毒感染组居住农村、有早产史、哮喘史患儿占比显著高于对照组(P<0.05);小儿呼吸道病毒感染时hs-CRP、IL-6、WBC水平升高,且居住农村、有早产史及哮喘史是小儿呼吸道病毒感染的危险因素(P<0.05);hs-CRP、IL-6、WBC及联合诊断小儿呼吸道病毒感染的曲线下面积AUC分别为0.644、0.885、0.617、0.923,联合诊断AUC显著高于单独检测(P<0.05)。结论 hs-CRP、IL-6、WBC在小儿呼吸道病毒感染患儿中水平较高,联合检测诊断价值较高。

Association of Interleukin-6-174G/C Polymorphism with the Risk of Diabetic Nephropathy in Type 2 Diabetes:A Meta-analysis

Previous studies reported the association between interleukin-6(IL-6)-174G/C gene polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus(T2DN).However,the results remain controversial.In the present study,we conducted a meta-analysis to further examine this relationship between IL-6-174G/C gene polymorphism and T2DN.Three databases(PubMed,SinoMed and ISI Web of Science)were used to search clinical case-control studies about IL-6-174G/C polymorphism and T2DN published until Apr.14,2018.Fixed-or random-effects n lodels were used to calculate the effect sizes of odds ratio(OR)and 95%confide nee intervals(95%CI).Moreover,subgroup analysis was performed in tenns of the excretion rate of albuminuria.All the statistical analyses were con ducted using Stata 12.0.A total of 11 case-control studies were included in this study,involving 1203 cases of T2DN and 1571 cases of T2DM without DN.Metaanalysis showed that there was an association between IL-6-174G/C polymorphism and increased risk of T2DN under the allelic and recessive genetic models(G vs.C:OR=1.10,95%CI 1.03-1」&P=0.006;GG vs.CC+GC:OR=1.11,95%CI 1.02-1.21,P=0.016).In the subgroup analysis by albuminuria,a significant association of IL-6-174G/C polymorphism with risk of T2DN was noted in the microalbuminuria group under the recessive model(OR=1.54,95%CI 1.02-2.32,P=0.038).In conclusion,this meta-analysis suggests that IL-6-174G/C gene polymorphism is associated with the risk of T2DN.

Interleukin-6 receptor blockade suppresses subretinal fibrosis in a mouse model

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.