Differential regulation of TNFα, IL-1β, IL-6, IL-8, TNFβ, and IL-10 by pentoxifylline

Pentoxifylline (PTX) is a methylxanthine drug known to inhibit the production of tumor necrosis factor-alpha (TNFα), which plays a key role in inflammation. Recent studies also revealed that other cytokines may be inhibited by PTX. We investigated PTX effects on production and mRNA expression of TNFα, IL-1β, IL-6, IL-8, TNFβ and IL-10. Cytokine release was studied in 1/10 diluted whole blood culture (WB) and in peripheral blood mononuclear cell (PBMC) culture. Cytokine production was triggered in both culture systems by endotoxin (LPS) or by phorbol ester (PMA) plus phytohemagglutinin (PHA). Our results showed that expression and production of TNFα and TNFβ were inhibited by PTX in a dose-dependent manner. Moreover, we observed that depending on the way of activating cells, PTX induced an up- or a down-regulation (in PMA+PHA or LPS stimulated cells, respectively) for IL-1 and IL-6 release. We also noted that the effects of PTX on IL-6, IL-8 and IL-10 production were different in WB and in PBMC culture. In conclusion PTX acts on cytokine in a complex manner depending on cellular environment and on the method of activation.     

慢性肝病患者血清IL-6,IL-8,IL-10含量变化

本文通过检测72例慢性肝病患者血清IL-6、IL-8、IL-10的含量变化,以探讨其在慢性肝病的早期诊断和疗效观察的意义,现将结果报告如下。     

不育症患者精浆IL-2,IL-6,IL-8,TNF-α测定的临床意义

目的 :观察精浆中白细胞介素 - 2 (IL - 2 )、白细胞介素 - 6 (IL - 6 )、白细胞介素 - 8(IL - 8)、肿瘤坏死因子 -α(TNF -α)等细胞因子对男性生殖的影响。方法 :应用放射免疫分析 (RIA)对 1 2 6例不育男性和 2 0例正常生育男性精浆IL - 2、IL - 6、IL - 8、TNF -α水平进行了检测。结果 :不育症组精浆IL - 2、IL - 6、IL -8、TNF -α含量均高于生育组 (p <0 0 5或 p <0 0 1 ) ;精浆中IL - 2、IL - 6、IL - 8、TNF -α含量在不育症组的WBC精液组与非WBC精液组之间均存在显著性差异 (p <0 0 5或 p <0 0 1 )。另外 ,精浆中TNF -α含量在精子活动力、活动率正常与减少之间 ,IL - 8含量在精子活动率正常与减少之间均存在显著性差异 (p <0 0 5或p <0 0 1 )。结论 :检测精浆中IL - 2、IL - 6、IL - 8、TNF -α等细胞因子的含量可以反映男性不育症患者的状态 ,帮助临床进行有价值的治疗     

冠心病患者TNF-α,IL-1β,IL-6,IL-8的变化研究

目的 :对冠心病患者血清中肿瘤坏死因子 (TNF -α)、白介素 - 1β(IL - 1β)、白介素 - 6 (IL - 6 )、白介素 - 8(IL - 8)含量进行分析 ,以探讨它们在冠心病发病过程中的意义。方法 :研究对象为正常对照组 36例 ,稳定型心绞痛组 32例 ,心肌梗塞组 39例 ,采用化学发光酶分析法检测其血清TNF -α、IL - 1β、IL - 6、IL - 8水平。结果 :与正常组比较 ,冠心病患者中TNF -α、IL - 1β、IL - 6、IL - 8水平均有不同程度升高 ,尤以心肌梗塞组升高明显 ,其差别有显著临床意义。心绞痛组TNF -α(p <0 0 5 ) ,IL - 6 (p <0 0 1) ,IL - 8(p <0 0 5 )。心肌梗塞组TNF -α(p<0 0 1) ,IL - 1β(p<0 0 5 ) ,IL - 6 (p <0 0 0 1) ,IL - 8(p <0 0 0 1)。 结论 :TNF -α、IL - 1β、IL - 6、IL- 8与动脉粥样硬化和冠心病的发生有密切关系 ,这些细胞因子可通过相互诱导、相互协同共同参与冠心病的发生、发展过程     

Blood Serum Levels of IL-2, IL-6, IL-8, TNF-α and IL-1β in Patients on Maintenance Hemodialysis

Cytokines are essential mediators of immune response and inflammatory reactions. Patients with chronic renal failure (CRF) commonly present with abnormalities of immune function related with impaired kidney function and the accumulation of uremic toxins in addition to bioincompatibility of dialyzer membranes. During a hemodialysis (HD) session, cytokines are released mainly by monocytes activated by endotoxin-type compounds in dialyzer fluid, complement factors and direct contact with dialyzer membrane. The study included 15 CRF patients, aged 36.4±2.9 years, on regular HD maintenance therapy for mean 68±10 months and 15 healthy controls. It was designed to assess serum levels of a panel of inflammatory cytokines: IL-1β, IL-2, IL-6, IL-8 and TNF-αin CRF patients on regular maintenance HD before, 20, 60 and 240 minutes of a single HD session in parallel with C-reactive protein (CRP) as an additional parameter. CRP concentration was increased in HD patients when compared with healthy controls. The concentrations of IL-1, IL-6, IL-8 and TNF-αwere increased, whereas the serum level of IL-2 was not altered during a single HD session.     

丙型肝炎患者血清TNF,IL-6,IL-10及其临床意义

目的 :探讨了丙型肝炎患者血清中TNF、IL - 6、IL - 10水平及意义。方法 :分别应用ELISA法和放免法检测了 5 8例丙型肝炎患者血清中TNF、IL - 6、IL - 10水平 ,并与 35名正常健康人作比较。结果 :丙型肝炎患者血清中TNF、IL - 6、IL - 10水平均非常显著地高于正常人水平 (P <0 .0 1) ,肝硬化组为甚 ,且TNF与IL - 6、IL - 10呈正相关 (r =0 .6 135 ,0 .6 2 2 5 ,P <0 .0 1)。结论 :TNF、IL - 6、IL - 10在丙型肝炎病毒感染的致病机理中有一定的临床价值。     

Evaluation of serum levels of IL-6, TNF-α, IL-10, IL-2 and IL-4 in patients with chronic hepatitis

Background

Changes in various cytokine activities have been reported during both HBV and HCV infections, while an imbalance of pro-inflammatory and anti-inflammatory cytokine production influences their immunopathogenesis. The aims of the present study are (a) to measure serum levels of interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), interleukin-10 (IL-10), interleukin-2 (IL-2) and interleukin-4 (IL-4) in a sample of patients affected either by chronic HBV infection or by chronic HCV infection and in healthy controls (b) to correlate serum levels of IL-6, TNF-α, IL-10, IL-2 and IL-4 with biochemical markers of liver disease and (c) to evaluate differences of the aforementioned cytokines between HBV and HCV patients, as well as between patients and healthy controls.

Methods

The study population consisted of 50 patients with chronic hepatitis B, 40 patients with chronic hepatitis C and 30 healthy controls aged between 28 and 75 years. Biochemical markers of liver disease were evaluated by routine methods approved by IFCC. Serum concentrations of IL-6, TNF-α, IL-10, IL-2 and IL-4 were determined with the Human Cytokine/Chemokine Panel I Merck Millipore.

Results

HBV patients showed statistically significant difference in TNF-α and IL-2 levels, versus healthy controls. HCV patients showed statistically significant difference in TNF-α, IL-10 and IL-2 levels versus healthy controls. IL10 and IL-2 levels were significantly different between HBV and HCV patients.

Conclusions

This study evaluated the serum cytokine levels (IL-6, TNF-α, IL-10, IL-2 and IL-4) of chronic hepatitis B or C patients, as well as the differences in such levels between patients and healthy controls. Correlations of cytokine levels with biochemical markers of liver disease were also observed, reflecting the degree of activity of the inflammatory process in the liver.     

银屑病患者血TNF-α,IL-6,IL-8水平观察

近年的研究表明 ,免疫调节功能异常在银屑病的发病中起着十分重要的作用 ,特别是细胞免疫抑制 ,体液免疫亢进 ,产生过量的抗原抗体复合物 ,继发免疫反应 ,造成细胞免疫调节异常[1] 。本文报道银屑病患者治疗前后血ＴＮＦ -α、ＩＬ -6、ＩＬ - 8水平检测结果。对象和方法一、对象 :(一 )正常人 :30人。均为我院预防保健科体检合格的健康人 ,无心、肝、肺、肾重要脏器疾患 ,肝、肾功能试验正常 ,均无皮肤病疾患。(二 )病人组 :33人。均为我院皮肤科明确诊断的银屑病患者 ,病程 1个月～ 15年 ,其中进行期 2 0例、静止期 13例 ,均排除高血压、…     

肺癌患者血浆IL-2,IL-6检测的临床意义

本文报道肺癌患者血浆ＩＬ - 2、ＩＬ - 6检测的结果 ,并就临床价值作初步探讨。对象和方法一、对象 :(一 )正常人 :35人。均为我院预防保健科合格的健康人 ,无心、肝、肺、肾等重要脏器疾患 ,肝肾功能试验正常。(二 )肺癌病人 :33人。均为我院临床上明确诊断的肺癌患者 ,全部病例均经Ｘ线、ＣＴ ,部分病例经核磁共振 ,最后由病理切片进一步地明确诊断 ,其中鳞癌 1 0例 ,小细胞癌 1 4例 ,腺癌 9例。二、方法 :(一 )标本收集 :受检者清晨空腹抽血后 ,低温下分离血浆 ,- 2 0℃保存 ,待检。(二 )ＩＬ - 2、ＩＬ - 6的测定 :放射免疫分析试剂盒…     

脑膜炎患儿CSF中IL-2,IL-8,TNF-α检测的临床意义

为观察脑膜炎患儿脑脊液 (ＣＳＦ)中白细胞介素 - 2 (ＩＬ - 2 )、白细胞介素 - 8(ＩＬ - 8)和肿瘤坏死因子 -α(ＴＮＦ -α)的变化 ,自1999年 8月～2 0 0 1年 3月 ,我们对 10 3例脑膜炎患儿ＣＳＦ中的ＩＬ- 2、ＩＬ - 8、ＴＮＦ -α进行了检测 ,现将结果报告如下。材料和方法一、一般材料 :10 3例患儿 (男 5 6 ,女 47) ,年龄 2月～ 9岁 ,平均 2 6± 1 8岁。全部患儿均为我院住院患者 ,并根据病史、临床症状、体征、ＣＳＦ实验室检查等资料确诊。其中病毒性脑膜炎 (病脑 ) 38例 ,结核性脑膜炎 (结脑 ) 34例 ,化脓性脑膜炎(化脑 ) 31例。另…     

Serum Levels of IL-6, IL-10, IL-12, IL-17 and IFN-γ and Their Association with Markers of Bone Metabolism in Vitamin D-Deficient Female Students

Different studies have shown the regulatory effects of vitamin D₃ on the immune system and bone metabolism. Regarding the effects of vitamin D on immune cells and the importance of cytokines on bone metabolism, we assessed the association between serum levels of interleukin (IL)-6, IL-10, IL-12, IL-17 and IFN-γ cytokines and bone metabolism markers (Ca, P, PTH, ALP) in female students with vitamin D deficiency compared with control group. A total of 100 subjects with 25-hydroxy vitamin D₃ (25-(OH) D₃) deficiency were selected as case and 100 subjects with sufficient 25-hydroxy vitamin D₃ (25-(OH) D₃) were selected as the control group. The serum levels of IL-6, IL-10, IL-12, IL-17 and IFN-γ were measured by ELISA method. Ionized Ca, PTH, P, ALP levels were also determined in all participants. The results showed a statistically significant positive correlation between the levels of ALP with IFN-γ, PTH with IL-17 and a significant negative correlation between P with IL-10 in vitamin D deficient group. The results suggest that IL-17, IFN-γ and IL-10 are important mediators of bone metabolism and vitamin D affect bone metabolism, at least in part, through immune system. In addition, not only vitamin D affect bone metabolism but also modulates immune responses.     

IL-2, IFN-γ, and IL-12 Gene Polymorphisms and Susceptibility to Multiple Sclerosis

Background  

Multiple sclerosis (MS) is a multifactorial disease. Positive genetic background could predispose individuals to this chronic disabling disease. In order to investigate the role of some proinflammatory cytokines (interleukin (IL)-2, IL-12, and interferon-gamma (IFN-γ)) as a risk factor for MS, this study was performed.     

小鼠抗CD_3单抗激活的T细胞增殖中IL-1,IL-2,IL-6的级联相关作用

通过自体辅佐细胞(单核或巨噬细胞)提呈处理过的抗原作用于TcR 可激活T 细胞。作用于TcR CD_3复合物的单抗可模拟这种抗原激活效应。作者使用仓鼠抗小鼠单抗145-2 C11,它结合于CD_3复合体上25-KDa的ε链上,从而激活T 细胞增殖。本实验研究了严格去除辅佐细胞的T 细胞在不同浓度培养下,用抗CD_3单抗激活的条件,包括辅佐细胞浓度、二价和多价抗CD_3单抗及细胞因子IL-1、IL-2、IL-6在T 细胞活化增殖     

Comparative quantification of IL-1?, IL-10, IL-10r, TNFa and IL-7 mRNA levels in UV-irradiated human skin in vivo

OBJECTIVE AND DESIGN: Ultraviolet (UV) exposure induces local immunosuppression and inflammation in human skin. Cytokines are, in part, responsible for these responses. To investigate the effects of UV-induced gene expression at the molecular level we established a sensitive in vivo/ex vivo method for a comparative quantification of cytokines and receptors involved in the local skin immune reactions. MATERIAL AND METHODS: Specific mRNA levels of human UV-irradiated skin were determined by real time quantification (TaqMan RT-PCR). Highly efficient PCR-reaction conditions were obtained by designing very short PCR-templates (72-87 bp). The most sensitive PCR-conditions were obtained by optimisation of primer and Mn(OAc)2-concentrations, which led to significant PCR signals (C(T)-value) of less than 36 cycles. A strong correlation between PCR efficiency of the internal control (GAPDH) compared to targets (IL-1beta, IL-10, IL-10r, TNFalpha, IL-7) allowed the use of deltadelta C(T)-method to quantify comparable mRNA levels. RESULTS: Interleukin-1beta (IL-1beta), Interleukin-10 (IL-10), and tumour necrosis factor alpha (TNFalpha) mRNA levels were increased in a time- and dose-dependent manner. Interleukin-1beta induction reached a maximum (approx. 44-fold) 6 h after a UV-dose equivalent to 3 times the minimal erythemal doses just perceptible (MEDjp). Maximal TNFalpha mRNA expression (approx. 14-fold) was also detected 6 h after UV exposure. Interleukin-10 mRNA induction reached a maximum of approximately 14-fold 24 h after UV-irradiation of 3 MEDjp. Time- and dose-dependent changes in Interleukin-7 and Interleukin-10 receptor mRNA levels did not occur after UV-irradiation. CONCLUSIONS: Time-distinct gene induction of IL-1beta, TNFalpha and IL-1beta is involved in UV-induced immune reactions, but no considerable changes were found for IL-10r or IL-7.     

IL-2,IL-6和IL-4在体外诱导细胞毒性T细胞中的作用

体外胸腺细胞分化为CTL需要抗原或促有丝分裂原的刺激.此外据报道IL-2,IL-4,IL-5,IL-6,IL-10,TNF及IFN-γ)也在此过程中起作用.CTL前体细胞(CTL-P)是不是某一IL的唯一靶细胞;是否不同亚群的T细胞先受刺激产生第二种介质依次最终导致CTL的分化,这些问题一直存在.为此,研究了IL-6诱导的ConA刺激后CD4~-CD8~+CTL-P分化的形式.结果发现,在去除了辅助细胞的胸腺细胞发育过程中,①rIL-1和rIL-6均可诱     

Serum levels of TGFβ, IL-10, IL-17, and IL-23 cytokines in β-thalassemia major patients: the impact of silymarin therapy

Several immunological abnormalities have been characterized in β-thalassemia, many of which are linked to or identified with cytokines. In this study, we investigated the serum levels of TGF-β, IL-10, IL-17 and IL-23 in β-thalassemia major patients in comparison with healthy controls. The immunomodulatory effect of silymarin (a flavonoid complex obtained from Silybum marinum) on the serum levels of cytokines was further evaluated in thalassemia patients receiving silymarin (420?mg/day) and compared with patients treated with placebo for 6-month. Serum cytokines levels were measured by enzyme linked immunosorbent assay (ELISA). The results showed a significant higher concentration of TGF-β and IL-23 in the patient group than control group. Among studied cytokines, a significant reduction in serum IL-10 levels was found in patients treated with silymarin when compared with IL-10 values at baseline. However, no significant difference was observed between baseline values of cytokine compared with end values in placebo group. Our data suggest the presence of imbalanced immune condition involving inflammation and immunosuppression in thalassemia patients, which could be modulated to a more effective immune response by silymarin.     

肝硬化患者血清HA,IL-12及IL-18检测的临床意义

本文报告肝硬化患者血清透明质酸 (ＨＡ) ,白细胞介素- 12 (ＩＬ - 12 )和白细胞介素 - 18(ＩＬ - 18)含量 ,并就临床价值进行初步探讨 ,以便为临床诊疗和预后提供依据 ,现报告如下。对象和方法一、对象 :(一 )正常人 :35人 (男 2 0 ,女 15 )。均为我院保健科健康体检合格的健康人 ,无心、肝、肺、肾等重要脏器疾患 ,肝、肾功能试验正常。年龄 2 5～ 36岁 ,平均 30 2岁。(二 )病人组 :6 2人 (男 4 2 ,女 2 0 )。均为我院从 2 0 0 0～2 0 0 2年经临床明确诊断的肝硬化患者 ,其中肝硬化无腹水组32人 ,肝硬化伴腹水组 30人 ,年龄 2 1～ 33岁 ,…     

Biologics targeting IL-5, IL-4 or IL-13 for the treatment of asthma – an update

Introduction: The development of monoclonal antibody-based biologics targeted at inhibition of the Th2 cytokines IL-4, IL-5 and IL-13 represent potentially effective treatments for patients with the glucocorticoid refractory eosinophilic asthma phenotype.

Areas covered: Asthma exhibits marked heterogeneity both clinically and at the molecular phenotypic level, requiring specifically targeted treatments to block the key pathways of the disease. It is becoming apparent that significant clinical effects with anti-cytokine-based biologic therapies are more likely in carefully selected patient populations that take asthma phenotypes into account. The development of reproducible and straightforward discriminatory biomarkers may aid identification of those patients most likely to benefit from treatment with these expensive interventions. This narrative review is based on English-language original articles in PubMed or Med-Line that reported significant clinical findings published in the last two years on the evidence demonstrating the effectiveness or otherwise of the targeting of IL-4, IL-5, or IL-13 in carefully selected patients with severe refractory asthma.

Expert commentary: The use of a baseline peripheral blood eosinophilia as a simple reproducible biomarker to identify patients with particular sub-phenotypes of asthma to guide the effective use of biologic therapy represents a significant step forward.