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.

Analyze interleukin-1β,interleukin-6,and tumor necrosis factor-αlevels in dry eye and the therapeutic effect of cyclosporine A

BACKGROUND Dry eye is a common eye disease.Artificial tears supplements are widely used for the treatment of dry eyes.However,multiple adverse effects have been observed in patients receiving long-term treatment with artificial tears,which may affect the therapeutic effect.AIM To analyze the characteristics of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-alpha(TNF-α)levels in patients with dry eye and the therapeutic effect of artificial tears combined with cyclosporine A.METHODS A total of 124 dry eye patients treated at The First People’s Hospital of Xining from April 2020 to April 2022 were selected as the observation group,while 20 healthy individuals served as the control group during the same period.Levels of inflammatory markers,including IL-1β,IL-6,and TNF-α,were analyzed.The observation group was further divided into a study group and a control group,each consisting of 62 patients.The control group received artificial tears,whereas the study group received a combination of artificial tears and cyclosporine A.Inflammatory markers,Schirmer’s test(SIT),tear break-up time(TBUT),corneal fluorescein staining(CFS),National Eye Institute Visual Function Questionnaire-25(NEI-VFQ-25)scores,and adverse events(AEs)were compared between the two groups.RESULTS The observation group exhibited significantly elevated serum levels of IL-1β,IL-6,and TNF-αin comparison to the healthy group.Following treatment,the study group demonstrated substantial reductions in IL-1β,IL-6,and TNF-αlevels relative to the control group.Moreover,after treatment,the study group experienced a marked decrease in CFS scores and significant increases in both SIT and BUT levels when compared to the control group.Additionally,significant improvements were observed in the primary symptom of dry eye and secondary symptoms such as photophobia,foreign body sensation,fatigue,red eye,and burning sensation within the study group.Furthermore,post-treatment NEI-VFQ-25 scores across all dimensions exhibited significant enhancements in the study group compared to the control group(P<0.05).It is noteworthy that significant AEs were reported in both groups throughout the treatment period.CONCLUSION Cyclosporine A combined with artificial tears is effective in treating dry eye,yielding enhanced outcomes by improving SIT and TBUT levels,reducing CFS scores,and ameliorating vision-related quality of life.

Exploring the role of interleukin-6 receptor blockade in epilepsy and associated neuropsychiatric conditions through a mendelian randomization study

BACKGROUND The interplay between inflammation,immune dysregulation,and the onset of neurological disorders,including epilepsy,has become increasingly recognized.Interleukin(IL)-6,a pro-inflammatory cytokine,is suspected to not only mediate traditional inflammatory pathways but also contribute to neuroinflammatory responses that could underpin neuropsychiatric symptoms and broader psychiatric disorders in epilepsy patients.The role of IL-6 receptor(IL6R)blockade presents an intriguing target for therapeutic intervention due to its potential to attenuate these processes.neuropsychiatric conditions due to neuroinflammation.METHODS Mendelian randomization(MR)analysis employing single nucleotide poly-morphisms(SNPs)in the vicinity of the IL6R gene(total individuals=408225)was used to evaluate the putative causal relationship between IL6R blockade and epilepsy(total cases/controls=12891/312803),focal epilepsy(cases/controls=7526/399290),and generalized epilepsy(cases/controls=1413/399287).SNP weights were determined by their effect on C-reactive protein(CRP)levels and integrated using inverse variance-weighted meta-analysis as surrogates for IL6R effects.To address potential outlier and pleiotropic influences,sensitivity analyses were conducted employing a variety of MR methods under different modeling assumptions.RESULTS The genetic simulation targeting IL6R blockade revealed a modest but significant reduction in overall epilepsy risk[inverse variance weighting:Odds ratio(OR):0.827;95%confidence interval(CI):0.685-1.000;P=0.05].Subtype analysis showed variability,with no significant effect observed in generalized,focal,or specific childhood and juvenile epilepsy forms.Beyond the primary inflammatory marker CRP,the findings also suggested potential non-inflammatory pathways mediated by IL-6 signaling contributing to the neurobiological landscape of epilepsy,hinting at possible links to neuroinflammation,psychiatric symptoms,and associated mental disorders.CONCLUSION The investigation underscored a tentative causal relationship between IL6R blockade and decreased epilepsy incidence,likely mediated via complex neuroinflammatory pathways.These results encouraged further in-depth studies involving larger cohorts and multifaceted psychiatric assessments to corroborate these findings and more thoroughly delineate the neuro-psychiatric implications of IL-6 signaling in epilepsy.The exploration of IL6R blockade could herald a novel therapeutic avenue not just for seizure management but also for addressing the broader psychiatric and cognitive disturbances often associated with epilepsy.

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.

Analysis of the Role of D-Dimer,Interleukin-6,and Interleukin-18 in Differential Diagnosis of Pediatric Refractory Mycoplasma pneumoniae Pneumonia

Objective:To analyze the value of D-dimer(D-D),interleukin-6(IL-6),and IL-18 in the differential diagnosis of children with refractory Mycoplasma pneumoniae pneumonia(RMPP).Methods:The medical records of 92 children with Mycoplasma pneumoniae pneumonia(MPP)treated in the hospital were selected for retrospective analysis from January 2023 to January 2024.After comprehensive examinations such as computed tomography examination of the chest,48 children with general Mycoplasma pneumoniae pneumonia(GMPP)were put in the GMPP group and 44 children with RMPP were grouped in the RMPP group.The IL-6,IL-18,and D-D levels were compared between the two groups,and the receiver operating characteristic(ROC)curves were plotted to analyze their value for differential diagnosis of RMPP.Results:The levels of IL-6,IL-18,and D-D in the RMPP group were higher than those in the GMPP group(P<0.05);the ROC curves showed that the specificity of the differential diagnosis of IL-6,IL-18,and D-D was higher,and their diagnostic value was significant.Conclusion:Determination of IL-6,IL-18,and D-D levels in children with MPP can further diagnose the children’s condition,which can help physicians formulate targeted treatment plans,and is of great significance to the improvement of the children’s condition,which is worthy of attention.

Efficacy of Laparoscopic Cholecystectomy in Treating Patients with Gallstones and Its Effect on Interleukin-6 and Tumor Necrosis Factor-α Levels

Objective:To investigate the efficacy of laparoscopic cholecystectomy in the treatment of patients with gallstones and its effect on the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-a).Methods:A total of 82 patients with gallstones admitted from July 2020 to July 2023 were recruited and allocated into control and observation groups using the random number table method,with 41 cases in each group.The patients were treated with laparoscopic cholecystectomy,with the anterior triangle anatomical approach to the gallbladder in the control group and the posterior triangle anatomical approach to the gallbladder in the observation group.The treatment effect and inflammatory factor levels of both groups were observed and compared.Results:When comparing the clinical outcomes of both patient groups,the key parameters evaluated included time to mobilization,duration of surgery,extubation time,and intraoperative bleeding.The observation group exhibited a significant advantage in these parameters compared to the control group(P<0.05).Regarding the levels of inflammatory factors between the two groups before and after treatment,there was no significant difference in values before treatment.However,following treatment,patients in the observation group showed significantly lower levels of IL-6,TNF-α,and C-reactive protein(CRP)compared to the control group(P<0.05).Conclusion:Patients undergoing laparoscopic cholecystectomy for gallstones can benefit from the implementation of the posterior triangular anatomical approach to the gallbladder,which not only enhances therapeutic efficacy but also offers significant advantages in reducing levels of IL-6,TNF-α,and CRP.Therefore,it is recommended for the widespread adoption of this treatment approach in clinical practice.

溃疡性直肠炎患者血清中Resistin水平及其与CRP和IL-6的相关性研究

目的探究溃疡性直肠炎患者血清中抵抗素(Resistin)的水平及其与C反应蛋白(CRP)、白介素-6(IL-6)的相关性。方法选取2014年9月-2015年9月收治我院经内镜证实的120例溃疡性直肠炎患者血清样本(试验组)和同期研究选取我院体检中心的120例健康体检者血清样本(对照组),并采用酶联免疫吸附(ELISA)检测患者血清中Resistin与CRP、IL-6的水平,分析指标间的相关性。结果与对照组相比,溃疡性直肠炎患者血清中Resistin,CRP,IL-6的水平明显升高(P<0.05),并且随着疾病病情严重程度的增加而升高;溃疡性直肠炎患者血清Resistin与CRP,IL-6呈相关(r=0.425,P=0.021;r=0.631,P=0.013)。结论溃疡性患者血清中Resistin的水平明显升高,并且与血清中CRP,IL-6和疾病病情的严重程度相关。指标的联合检测有利于对溃疡性直肠炎疾病病情的判断。

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

Glutamine-supplemented total parenteral nutrition attenuates plasma interleukin-6 in surgical patients with lower disease severity

AIM： To evaluate whether the effect of Gin dipeptideenriched total parenteral nutrition （TPN） on postoperative cytokine alteration depended on the disease severity of surgical patients. METHODS： Forty-eight patients with major abdominal surgery were allocated to two groups to receive isonitrogenous （0.228 g nitrogen/kg per d） and isocaloric （30 kcal/kg per d） TPN for 6 d. Control group （Cony） using conventional TPN solution received 1.5 g amino acids/kg per day, whereas the test group received 0.972 g amino acids/kg per day and 0.417 g L-alanyI-L-glutamine （Ala-GIn）/kg per day. Blood samples were collected on d 1 and d 6 postoperatively for plasma interleukin （IL）-2, IL-6, IL-8, and interferon （IFN）-γ analysis. RESULTS： Plasma IL-2 and IFN-γ were not detectable. IL-6 concentrations were significantly lower on the 6^th postoperative day in the Ala-GIn group than those in the Cony group in patients with APACHE Ⅱ≤6, whereas no difference was noted in patients with APACHE Ⅱ〉6. There was no difference in IL-8 levels between the two groups. No difference in cumulative nitrogen balance was observed on d 2-5 after the operation between the two groups （Ala-GIn -3.2±1.6 g vs Cony -6.5±2.7 g）. A significant inverse correlation was noted between plasma IL-6 levels and cumulative nitrogen balance postoperatively in the Ala-GIn group, whereas no such correlation was observed in the Conv group. CONCLUSION： TPN supplemented with Gin dipeptide had no effect on plasma IL-8 levels after surgery. However, Gin supplementation had a beneficial effect on decreasing systemic IL-6 production after surgery in patients with low admission illness severity, and lower plasma IL-6 may improve nitrogen balance in patients with abdominal surgery when Gin was administered.