Diagnostic value of serum vascular endothelial growth factor and interleukin-17 in primary hepatocellular carcinoma

BACKGROUND Despite significant advancements in the medical treatment of primary hepato-cellular carcinoma(PHC)in recent years,enhancing therapeutic effects and im-proving prognosis remain substantial challenges worldwide.AIM To investigate the expression levels of serum vascular endothelial growth factor(VEGF)and interleukin(IL)-17 in patients with PHC and evaluate their diagnostic value while exploring their relationship with patients’clinical characteristics.METHODS The study included 50 patients with confirmed PHC who visited Wuhan Han-yang Hospital from January 2021 to January 2022,and 50 healthy individuals from the same period served as the control group.Serum VEGF and IL-17 levels in both groups were measured by Enzyme-Linked Immunosorbent Assay,and their diagnostic value was assessed using receiver operating characteristic(ROC)curves.Pearson correlation analysis was performed to examine the relationship between serum VEGF and IL-17 levels.Pathological data of the PHC patients were analyzed to determine the relationship between serum VEGF and IL-17 levels and pathological characteristics.RESULTS Serum VEGF and IL-17 levels were significantly higher in the study group com-pared to the control group(P<0.05).No significant association was observed between serum VEGF and IL-17 levels and gender,age,combined cirrhosis,tumor diameter,or degree of differentiation(P>0.05).However,there was a significant relationship between clinical TNM stage,tumor metastasis,and serum VEGF and IL-17 levels(P<0.05).Correlation analysis revealed a positive correlation between serum VEGF and IL-17(P<0.05).ROC analysis demonstrated that both serum VEGF and IL-17 had good diagnostic efficacy for PHC.CONCLUSION Serum VEGF and IL-17 levels were significantly higher in PHC patients compared to healthy individuals.Their levels were closely related to pathological features such as tumor metastasis and clinical TNM stage,and there was a significant positive correlation between VEGF and IL-17.These biomarkers may serve as valuable reference in-dicators for the early diagnosis and treatment guidance of PHC.

Interleukin-17 SNPs and serum levels increase ulcerative colitis risk: A metaanalysis

AIM: To investigate the associations of interleukin-17 (IL-17) genetic polymorphisms and serum levels with ulcerative colitis (UC) risk.

老年急性脑梗死患者血清Del-1和IL-17水平变化及与梗死面积和预后的关系

目的 探究老年急性脑梗死(ACI)患者血清内皮发育调节基因-1(Del-1)、白细胞介素-17(IL-17)水平与脑梗死面积、病情严重程度及预后的关系。方法 回顾性收集2019-01-2021-12厦门大学附属东南医院收治的126例老年ACI患者(病例组)及105名健康体检者(对照组)的临床资料,根据脑梗死面积将病例组患者分为大面积梗死组(梗死最大直径>5 cm,n=14)、中面积梗死组(梗死最大直径3~5 cm,n=53)和小面积梗死组(梗死最大直径<3 cm,n=59);根据NIHSS评分分为重症组(NIHSS评分≥16分,n=13)、中症组(5分<NIHSS评分<15分,n=58)和轻症组(NIHSS评分≤5分,n=55);根据m RS评分分为预后良好组(mRS评分≤2分,n=81)和预后不良组(mRS评分>2分,n=45)。采用荧光免疫法检测血清Del-1、IL-17水平,受试者工作特征(ROC)曲线评估血清Del-1、IL-17水平预测老年ACI患者预后的价值。结果 病例组吸烟史比例、收缩压、舒张压、糖化血红蛋白、血清IL-17水平均高于对照组,血清Del-1水平低于对照组(P<0.05)。不同脑梗死面积患者血清Del-1水平比较,小面积梗死组>中面积梗死组>大面积梗死组;血清IL-17水平比较,小面积梗死组<中面积梗死组<大面积梗死组(P<0.05)。轻症组血清Del-1水平高于中症组、重症组(P<0.05),不同病情严重程度患者血清IL-17水平比较,重症组>中症组>轻症组(P<0.05)。预后良好组患者血清Del-1水平高于预后不良组,血清IL-17水平低于预后不良组(P<0.05)。ROC曲线分析显示,血清Del-1、IL-17预测ACI患者预后的AUC值分别为0.763、0.747(P<0.05)。结论 老年ACI患者血清Del-1水平较低,IL-17水平较高,二者与患者脑梗死面积、病情严重程度和预后关系密切,可作为预测老年ACI患者预后的可靠指标。

内镜射频治疗反流性食管炎的疗效及对血清G-17、PGI、PGⅡ水平的影响

目的探究内镜射频治疗反流性食管炎的疗效及对血清胃泌素-17(G-17)、胃蛋白酶原I(PGI)、胃蛋白酶原Ⅱ(PGⅡ)水平的影响。方法选取安阳市人民医院2021年11月至2022年12月收治的126例反流性食管炎患者为研究对象,根据患者的治疗方法将其分为药物组(n=48)和射频组(n=78)。药物组采用艾司奥美拉唑进行治疗,射频组采用内镜射频进行治疗。比较两组的疗效;比较两组的临床症状[泛酸、胸骨后灼痛、进食梗阻感]消失时间;比较两组治疗前后的血清学指标[G-17,PGI,PGⅡ]水平;比较治疗后两组的生活质量和睡眠质量评分。结果射频组的总有效为89.74%,高于药物组的75.00%,差异有统计学意义(χ^(2)=4.837,P<0.05)。射频组的泛酸、胸骨后灼痛、进食梗阻感消失时间均低于药物组,差异有统计学意义(t=3.083、2.750、2.348,P<0.05)。治疗后,两组的G-17、PGⅡ均低于治疗前,且射频组低于药物组,差异有统计学意义(t=4.372、2.157,P<0.05);PGI水平均高于治疗前,且射频组高于药物组,差异均有统计学意义(t=4.372、2.157、2.449,P<0.05)。射频组的生活质量评分高于药物组,睡眠质量评分低于药物组,差异有统计学意义(t=3.165、2.473,P<0.05)。结论内镜射频治疗反流性食管炎具有较高的疗效,可以有效减少患者的临床症状消失时间,改善其血清G-17,PGI,PGⅡ水平,提高睡眠质量和生活质量,具有较高的临床应用价值。

Interleukin-17 levels in Helicobacter pylori-infected gastric mucosa and pathologic sequelae of colonization

AIM： To determine the role of interleukin （IL）-17 in gastric ulcerogenesis. METHODS： Thirty-six gastric ulcer （GU） patients and 29 non-ulcer （NU） patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used in in situ stimulation for 48 h in the presence of 10 ug/mL phytohemagglutinin-P （PHA）, histological examination, and Helicobacter pylori（Hpylon） culture. IL-17 and IL-8 protein levels in culture supematants were assayed by ELISA. IL- 17 mRNA expression was analyzed by reverse transcriptasepolymerase chain reaction （RT-PCR）. Hpylori cagA and vacA status was assessed by reverse hybridization using a line probe assay （UPA）. IL-8 levels in culture supematants were assayed after AGS cells were co-cultured with Hpylori strain 26 695 or recombinant human （rh） IL-17. RESULTS： All 36 GU patients and 15 of 29 NU patients were found to be Hpy/or/-positive, while 14 NU patients were Hpylori-nogative. All 51 H pylori strains from both GU and NU patients were cagA- and vacAsl/ml-positive. Antral mucosal tissues from H pylori-positive patients contained significantly （H pylori-positive NU patients： median 467 pg/mg/protein, range 53-2 499; Hpylori negative NU patients： median 104 pg/mg/protein, range 16-312, P〈0.0005） higher levels of IL-17 than those from uninfected patients. IL-17 levels at the ulcer site were significantly （ulcer site： median 1 356 pcj/mg/protein, range 121-1 3730; antrum： median 761 pg/mg/protein, range 24-7 620, P〈0.005） higher than those at distant sites in the antrum. Biopsies from H pylori-positive GU and NU patients showed IL-17 mRNA expression in all samples whereas those from the antrum of the Hpylori-negativecontrols showed no detectable expression. A significant correlation was seen between IL-17 and IL-8 levels at each biopsy site （ulcer： r = 0.62,P〈0.0001; antrum： r = 0.61, P〈0.0001） in GU patients. RhIL-17 and Hpylori strain 26 695 each stimulated IL-8 production from AGS cells. CONCLUSION： IL-17 may play an important role in the inflammatory response to Hpyloricolonization, and may ultimately influence the outcome of H pylori-associated diseases that arise within the context of gastritis.

Role of serum interleukin-18 as a prognostic factor in patients with hepatocellular carcinoma

AIM:To determine whether serum interleukin-18 (IL-18) levels correlated with clinicopathologic features and prognosis in patients with hepatocellular carcinoma (HCC). METHODS:Serum IL-18,IL-6 and IL-12 levels were measured by enzyme-linked immunosorbent assay (ELISA) from 70 patients with HCC and 10 healthy controls. RESULTS:Serum IL-18,IL-6 and IL-12 levels of patients with HCC were significantly higher that those of the controls. The levels of IL-18 correlated significantly with the presence of venous invasion and advanced tumor stages classified by Okuda's criteria. Patients with high serum IL-18 levels (≥ 105 pg/mL) had a poorer survival than those with low serum IL-18 levels (< 105 pg/mL) (4 and 11 mo,respectively,P = 0.015). Multivariate analyses showed that serum IL-18 level,but not IL-6 and IL-12 levels,was a significant and independent prognostic factor of survival. CONCLUSION:These findings demonstrate that serum IL-8 may a useful biological marker of tumor invasiveness and an independent prognostic factor of survival for patients with HCC. Thus,the detailed mechanisms of IL-18 involving in tumor progression should be further investigated.

Vitamin D deficiency: Correlation to interleukin-17, interleukin-23 and PⅢNP in hepatitis C virus genotype 4

AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response mediators. METHODS: The study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the Endemic Disease Hospital at Cairo University. Patients were compared with 25 ageand sexmatched healthy individuals. Inclusion criteria were based on a history of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under followup). Based on ultrasonography, patients were classified into four subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC).Total Vit D (i.e., 25-OH-Vit D) and active Vit D [i.e., 1,25-(OH) 2 -Vit D] assays were carried out using commercial kits. IL-17, IL-23 and PⅢNP levels were assayed using enzyme linked immunosorbent assay kits, while HCV virus was measured by quantitative and qualitative polymerase chain reaction. RESULTS: Levels of Vit D and its active form were significantly lower in advanced liver disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PⅢNP levels were markedly increased in HCV patients and correlated with the progression of hepatic damage. The decrease in Vit D and active Vit D was concomitant with an increase in viral load, as well as levels of IL-17, IL-23 and PⅢNP among all subgroups of HCV-infected patients, compared to normal healthy controls. A significant negative correlation was evident between active Vit D and each of IL-17, IL-23 and PⅢNP (r = -0.679, -0.801 and -0.920 at P < 0.001, respectively). HCV-infected men and women showed no differences with respect to Vit D levels. The viral load was negatively correlated with Vit D and active Vit D (r = -0.084 and -0.846 at P < 0.001, respectively), and positively correlated with IL-17, IL-23 and PⅢNP (r = 0.951, 0.922 and 0.94 at P < 0.001, respectively). Whether the deficiency in Vit D was related to HCVinduced chronic liver disease or was a predisposing factor for a higher viral load remains to be elucidated. CONCLUSION: The negative correlations between Vit D and IL-17, IL-23 and PⅢNP highlight their involvement in the immune response in patients with HCV-4related liver diseases in Egypt.

Interleukin-17 plays a critical role in the acute rejection of intestinal transplantation

AIM:To investigate the role of interleukin(IL)-17 in small bowel allograft rejection.METHODS:We detected the expression of helper T cell 17(Th17)cells in biopsy specimens from 3 cases of living small bowel transplantation in our department through immunofluorescence stain.We then established a rat heterotopic small bowel transplantation model.The rats were sacrificed on the 1st,2nd,3rd,5th, and 7th d after small bowel transplantation.The degrees of transplantation rejection in rat intestine graft were examined through hematoxylin eosin(HE)stain, and the expression of Th17 cells in rat intestine graft were detected through immunofluorescence stain. In addition,the recipient rats undergoing intestinal transplantation were administrated with mouse-anti-rat IL-17 monoclonal antibody(mAb),and the survival of rats was analyzed.The recipient rats which received mouse-anti-rat IL-17 mAb treatment were sacrificed on the 1st,2nd,3rd,5th,and 7th d after small bowel transplantation.The degrees of transplantation rejection and the expression of Th17 cells in rat intestine graft were detected through HE and immunofluorescence stain. The expression of IL-17,IL-1β,tumor necroses factor receptor-α(TNF-α),IL-6,and IL-8 in the intestine graft or serum were also detected. RESULTS:The expressions of Th17 cells ran parallel with the degree of acute rejection in human intestine grafts.The intestine graft rejection of rats was aggravated with prolonged duration after intestinal transplantation,and the expressions of Th17 cells were also correlated with the degree of acute rejection in rat intestine grafts.Administration of mouse-anti-rat IL-17 mAb prolonged the survival of rats after small bowel transplantation(P<0.001).Furthermore,we found that the administration of mouse-anti-rat IL-17 mAb significantly decreased the intensity of CD4+IL-17+Th17 cells in intestine grafts on the 2nd,3rd,5th,and the 7th d (97.22±4.05vs 12.45±2.02 on the 7th d,P<0.0001), and suppressed the severity of acute rejection.The expression of IL-17 in the intestine graft declined after mouse-anti-rat IL-17 mAb administration on the 2nd,3rd,5th,and the 7th d(0.88±0.03 vs 0.35±0.02 on the 7th d,P<0.0001).We also detected the IL-17 serum level and found that the IL-17 level reduced from the 1st d to the 7th d(6.52±0.18 ng/mL vs 2.04±0.15 ng/mL on the 7th d,P<0.0001).No significant difference in the level of IL-17 mRNA in the intestine graft was identified between the two groups.The levels of IL-1β,TNF-α, IL-6,and IL-8 mRNA in the intestine graft after the administration of mouse-anti-rat IL-17 mAb were also tested.We found that on the 3rd,5th,and 7th d after intestinal transplantation,administration of mouse-anti- rat IL-17 mAb significantly inhibited the levels of IL-1β (12.11±1.16 vs 1.27±0.15 on the 7th d,P<0.001), TNF-α(27.37±2.60 vs 1.06±0.26 on the 7th d,P< 0.001),IL-6(21.43±1.79 vs 1.90±0.32 on the 7th d, P<0.001),and IL-8(20.44±1.44 vs 1.34±0.20 on the 7th d,P<0.001)mRNA in the intestine graft. CONCLUSION:IL-17 may act as a promising and potent target for inhibiting acute rejection after small bowel transplantation.

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.

Polymorphism in the interleukin-17A promoter contributes to gastric cancer

AIM:To evaluate the contribution of the G-197A polymorphism in the interleukin-17(IL-17)promoter region to gastric cancer risk in an Iranian population.METHODS:We performed a case control study using samples from 161 individuals with gastric cancer and171 healthy controls.For each individual,the G-197A genotype was determined by restriction fragment length polymorphism analysis of polymerase chain reaction-amplified fragments.Statistical analyses were performed to determine whether any demographic or behavioral factors,infection with Helicobacter pylori(H.pylori),or a particular G-197A genotype was associated with gastric cancer risk.RESULTS:We found that the G-197A genotype wassignificantly associated with increased gastric cancer risk(P=0.001).Patients who were homozygous(AA)at position-197 were 2.9 times more likely to develop disease(95%CI:1.56-5.4;P=0.001).Furthermore,logistic regression analysis revealed that the presence of a single A allele increased the risk of gastric cancer up to 1.7-fold(95%CI:1.26-2.369;P=0.001).This association was observed for early stage gastric adenocarcinomas only,and was not linked to H.pylori infection.CONCLUSION:These results suggest that carrying one or more G-197A polymorphisms at position-197 in the IL-17 promoter region significantly increases gastric cancer risk in this patient population.

Expression of Interleukin-17 in Lung and Peripheral Blood of Asthmatic Rats and the Influence of Dexamethasone

The expression of interleukin-17 （IL-17） in lung and peripheral blood of asthmatic rats and the influence of dexamethasone, and the role of IL-17 in the pathogenesis of asthma were investigated. Thirty Sprague-Dawley （SD） adult rats were randomly divided into three groups （n=10 in each group）： normal group, asthmatic group, and dexamethasone-interfered group. Rat asthmatic model was established by intraperitoneal （i.p.） injection of 10% ovalbumin （OVA） and challenge with 1% OVA via inhalation. Rats in dexamethasone-interfered group were pretreated with dexamethasone （2 mg/kg, i.p.） 30 min before each challenge. The expression of IL-17 protein in serum and bronchoalveolar lavage fluid （BALF） was detected by ELISA. The expression of IL-17 mRNA in peripheral blood mononuclear cells （PBMC） and BALF cells was semi-quantitatively detected by RT-PCR. The expression of IL-17 protein in serum and BALF of asthmatic rats was significantly elevated as compared with normal rats and dexamethsone-interfered rats （P〈0.01）, and there was significant difference between normal rats and dexamethsone-interfered rats （P〈0.05）. The expression of IL-17 mRNA in PBMC and BALF cells of asthmatic rats was markedly increased as compared with normal rats and dexamethsone-interfered rats （P〈0.01）, and significant difference was found between normal rats and dexamethsone-interfered rats （P〈0.05）. It was concluded that the expression of IL-17 was increased significantly in asthmatic rats and could be inhibited partly by dexamethasone, suggesting that IL-17 might play an important role in the pathogenesis of asthma as an inflammation regulation factor.

The Expression of Interleukin-17, Interferon-gamma, and Macrophage Inflammatory Protein-3 Alpha mRNA in Patients with Psoriasis Vulgaris

Summary: To investigate the role of Interleukin-17 (IL-17), Interferon-gamma (IFN-γ), and macrophage inflammatory protein-3 alpha (MIP-3α) in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to semi-quantitatively analyze the mRNA expression of IL-17, IFN-γ, and MIP-3α in 31 psoriatic lesions and 16 normal skin tissues. The results showed that the mRNA of the three cytokines was present in all specimens. And the expression level of IL-17 mRNA in skin lesions was 1.1416±0.0591, which was significantly higher than that in normal controls (0.8788±0.0344, P<0.001). The expression levels of IFN-γ mRNA were 1.1142±0.0561 and 0.9050±0.0263, respectively, with significant difference(P<0.001). And the expression levels of MIP-3α mRNA in psoriatic lesions was 1.1397±0.0521, which was markedly higher than that in normal controls (0.8681±0.0308, P<0.001). These findings indicate that up-regulated expression of IL-17, IFN-γ, and MIP-3α might be involved in the pathogenesis of psoriasis.

Unexpected alliance between syndecan-1 and innatelike T cells to protect host from autoimmune effects of interleukin-17

Innate-like T cells, namely natural killer T(NKT) and γδ T cells, play critical roles in linking innate and adaptive immune responses through rapid production of cytokines. Prominent among these cytokines is interleukin-17(IL-17), which is a potent proinflammatory cytokine that plays a critical role in host defense against fungi and extracellular bacteria. However, excessive IL-17-production promotes autoimmune diseases, including psoriasis, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus. IL-17 has also been implicated in regulating body fat, which is highly relevant given rises in obesity and type 2 diabetes. NKT cells, γδ T cells and mucosal-associated invariant T cells(MAIT) are the major sources of IL-17 involved in protection of mucosal surfaces from opportunistic infections and causing autoimmunity when become dysregulated. Given the pathogenic effects of IL-17, efforts have been directed towards understanding mechanisms that guard against IL-17 overproduction. One novel potent mechanism is mediated by the heparan sulfate proteoglycan, syndecan-1(sdc1), which is selectively expressed by IL-17-producing subsets of NKT and γδ T cells. This unexpected role for sdc1 is uncovered by analysis of NKT and γδ T cells in sdc1-deficient mice. In this mini-review, we discuss selective expression of sdc1 by these innate T cells and consequences of its absence on IL-17 homeostasis and pathological implications.

Suppressive effect of pectic polysaccharides extracted from Rauwolfia verticillata(Lour.) Baill.var.hainanensis Tsiang on inflammation by regulation of NF-κB pathway and interleukin-17 in mice with dextran sulphatesodium-induced ulcerative colitis

Objective:To investigate the effects of pectic polysaccharides extracted from Rauwolfia verticillata(Lour.) Baill.var.hainanensis Tsiang on an experimental murine colitis model.Methods:Experimental colitis was induced by dextran sulfate sodium(DSS),and mice were divided into 4 groups:control.DSS alone.DSS plus SASP,DSS plus pectic polysaccharides.The disease activity index(DAI) and histological score were observed.The tumor necrosis factor(TNF)-α and interleukin(IL)-17 levels were measured by enzyme-linked immunosorbent assay.I κ B and NF-κB p65 expression were assessed by western blot analysis.Myeloperoxidase(MPO) activity was determined by using MPO assay kit.Re.sults:Administration of pectic polysaccharides significantly reduced the severity of DSS-induced colitis as assessed by DAT and histological score,and resulted in down regulation of MPO activity and NF-κB p65 expression and subsequent degradation of IκB protein,strikingly reduced the production of TNF-α and IL-17.Conclusions:Pectic polysaccharides extracted from Rauvolfia verticillata(Lour.)Baill.var.hainanensis Tsiang exerts beneficial effects in experimental colitis and may therefore provide a useful therapeutic approach for the treatment of UC.

Regulation of the mesenchymal stem cell fate by interleukin-17: Implications in osteogenic differentiation

Bone regeneration is a tightly regulated process that ensures proper repair and functionality after injury.The delicate balance between bone formation and resorption is governed by cytokines and signaling molecules released during the inflammatory response.Interleukin(IL)-17A,produced in the early phase of inflammation,influences the fate of osteoprogenitors.Due to their inherent capacity to differentiate into osteoblasts,mesenchymal stem/stromal cells(MSCs)contribute to bone healing and regeneration.This review presents an overview of IL-17A signaling and the leading cellular and molecular mechanisms by which it regulates the osteogenic differentiation of MSCs.The main findings demonstrating IL-17A’s influence on osteoblastogenesis are described.To this end,divergent information exists about the capacity of IL-17A to regulate MSCs’osteogenic fate,depending on the tissue context and target cell type,along with contradictory findings in the same cell types.Therefore,we summarize the data showing both the pro-osteogenic and anti-osteogenic roles of IL-17,which may help in the understanding of IL-17A function in bone repair and regeneration.

Neutrophil-derived interleukin-17A participates in neuroinflammation induced by traumatic brain injury

After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury(sub-acute phase), genome-wide transcriptomic data showed that interleukin 17 A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17 A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17 A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17 A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17 A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17 A may be a promising therapeutic target for traumatic brain injury.

Interleukin-17A gene variants and risk of coronary artery disease:a large angiography-based study

Background Recent studies have also revealed that interleukin(IL)-17A plays a key role in atherosclerosis and its complication,but the relationship of its common variants with coronary artery disease(CAD) has not been extensively studied.Methods We systematically screened sequence variations in the IL17A gene and designed an angiog-raphy -based case-controlled study consisting of 1031 CAD patients and 935 control subjects to investigate the association between the selected polymorphisms of IL-17A gene and CAD risk in Chinese Han population.Results Frequencies of IL17A rs8193037 GG homozygote and G allele were significantly higher in the patient group than those in the control group(P【0.001;OR=0.68;95%CI=0.54-0.85).Stratification analysis showed that the IL17A rs8193037 G allele significantly increased the risk of CAD only among male subjects (P=0.001;OR=0.63;95%CI=0.47-0.83).After adjustment for conventional risk factors,binary logistic regression analysis showed that the G allele carriers(GG +AG) had significantly increased CAD risk compared with the AA homozygotes (adjusted P【0.001;OR 0.43;95%CI,0.33- 0.58).ELISA showed augmented IL17A production in plasma of the AMI patients.Conclusions Based on our data,we speculated that the SNP rs8193037 of IL17A gene is significantly associated with CAD risk in Chinese Han population and the rs8193037 G allele which is associated with increased expression of IL17A in AMI patients may be an independent predictive factor for CAD.

Interleukin-17 mediates liver progenitor cell transformation into cancer stem cells through downregulation of miR-122

Objective:Cancer stem cells(CSCs)have been the focus of several studies because oftheir involvement in cancer initiation and progression.CSCs were identified in 28%to 50%of hepatocellular carcinomas(HCCs).The origin of CSCs is still unclear,but it has been recently suggested that CSCs could originate from the transformation of liver progenitor cells(LPCs)during chronic liver inflammation.

SERUM INTERLEUKIN-18 LEVEL AS A PROGNOSTIC MARKER IN PATIENTS WITH COLORECTAL CARCINOMA

Interleukin-18(IL-18) is a cytokine with many functions. This study was to investigate the serum levels of IL-18 and their clinical significance in patients with colore3ctaql carcinomas. Methods: Peripheral blood samples were obtained from 106 patients with colorectal carcinoma and 60 volunteers. The serum IL-18 levels were determined in each sample with an enzyme-linked immunosorbent assay (ELISA). Results: In patients before 1997, the mean IL-18 level was 338.46 pg/ml; in patients after 1997, the mean IL-18 level was 328.85 pg/ml, there is no evidence of loss of IL-18 immunoreactivity after prolonged storage at -80℃. The mean serum IL-18 level in 106 patients with colorectal carcinoma was significantly higher compared with the 60 healthy volunteers (P<0.05). Although the IL-18 level in patients with stage I did not differ from controls, the serum IL-18 levels of patients with stage II, stage III and stage IV disease were significantly higher compared with healthy control (P<0.05). The mean serum IL-18 level of patients with stage III disease, while the difference between patients with stage II and stage IV was not statistically significant (P>0.05). The survival rate of patients with IL-18 levels ≥346 pg/ml (n=47 patients) was significantly worse compared with patients who had IL-18 levels <346 pg/ml(n=57 patients). The 5-year-survival rates were 5.3% and 18.6%, respectively. Multivariate analysis using a Cox proportional hazards model identified the serum IL-18 level as an independent prognostic factor for survival Conclusion: The serum IL-18 level has a significant correlation with survival curve. The serum IL-18 level may represent a significant postoperative prognostic determinant in patients with colorectal carcinoma.

Drug-induced entero-colitis due to interleukin-17 inhibitor use;capsule endoscopic findings and pathological characteristics:A case report

BACKGROUND Interleukin-17(IL-17)inhibitors are known to cause exacerbation or new onset of inflammatory bowel disease upon administration.However,few reports have described characteristic endoscopic and histopathologic findings,and no small intestinal lesions have been reported so far.CASE SUMMARY A woman in her 60s with psoriasis was administered ixekizumab(IXE),an anti-IL-17A antibody,for the treatment of psoriasis.Twenty months after commencing treatment,the patient visited our hospital because of persistent diarrhea.Blood tests performed at the time of the visit revealed severe inflammation,and colonoscopy revealed multiple round ulcers throughout the colon.A tissue biopsy of the ulcer revealed infiltration of inflammatory cells and granuloma-like findings in the submucosal layer.Capsule endoscopy revealed multiple jejunal erosions.After the withdrawal of IXE,the symptoms gradually improved,and ulcer reduction and scarring of the colon were endoscopically confirmed.CONCLUSION To the best of our knowledge,17 reports have documented IL-17 inhibitorinduced entero-colitis with endoscopic images,endoscopic findings,and pathological characteristics,including the present case.Nine of these cases showed diffuse loss of vascular pattern,coarse mucosa/ulcer formation in the left colon,and endoscopic findings similar to those of ulcerative colitis.In the remaining eight cases,discontinuous erosions and ulcerations from the terminal ileum to the rectum were seen,with endoscopic findings similar to those of Crohn’s disease.In this case,the findings were confirmed by capsule endoscopy,which has not been previously reported.