连续性血液净化对MODS患者IL-6、IL-10及肿瘤坏死因子的影响

目的 探讨连续性血液净化(CBP)对多脏器功能障碍综合征(MODS)患者细胞因子的影响.方法 CBP治疗后血BUN、SCr明显降低,血浆TNF-α、IL-6、IL-10水平显著下降.19例病人中TNF-α、IL-6、IL-10细胞因子的清除以6～24h清除最明显,CBP后36h增高,细胞因子清除与器官损伤多少无明显的相关性,前后时间IL-6、IL-10的下降率在这三个时间段(CBP治疗后2h和0h,CBP后2h和6h,CBP后24h和CBP后6h)变化间有差异,而在后面的时间变化上无差异.其中,IL-6在CBP治疗后2h与0h、CBP治疗后2h与CBP治疗后6h,这两个时间内下降高于IL-10;而IL-10仅在CBP治疗后24h与CBP治疗后6h,这两个时间之间下降高于IL-6.分别比较危重症和重症病人的细胞因子IL-6、IL-10无统计学意义.结果 ① MODS时血清IL-6、IL-10、TNF-α均有明显的增高.但是抗炎因子的IL-10释放迟于IL-6的释放.早期以促进炎症反应为主,晚期以抗炎反应占优势.二者的失衡导致了MODS的发展.②连续性血液净化对MODS有保护作用.③连续性血液净化能有效的清除细胞因子IL-6、IL-10及TNF-α,且以CBP后6～24h清除最为显著,临床上,第二次连续性血液净化的时间最好是在第一次后24～36h之间.④ CBP的应用能显著降低血清中抗炎和促炎细胞因子水平,IL-6与IL-10的清除率在2、6、24h有显著意义.其中在CBP后6h内以清除促炎因子IL-6为主,在CBP后24h以清除抗炎因子IL-10为主,清除细胞因子的多少与脏器功能损伤的多少无相关性.⑤ CBP能减少器官的损伤,降低致残率.改善肺氧和功能,改善生化功能,明显提高MODS患者的生存率.结论 ①MODS时血清IL-6、IL-10、TNF-α均有明显的增高.但是抗炎因子IL-10释放迟于IL-6的释放,早期以促进炎症反应为主.晚期以抗炎反应占优势.二者的失衡导致了MODS的发生发展.连续性血液净化对MODS有保护作用.②连续性血液净化能有效的清除细胞因IL-6、IL-10、TNF-α,且以CBP后6-24h清除最为显著,临床上第一次CBP后,第二次连续性血液净化的时间最好是24～36h之间进行.③CBP的应用能显著降低血清中抗炎和促炎症因子水平,其中促炎因子和抗炎因子的清除下降率:IL-6与IL-10两者的下降率在2、6、24h均下降.其中在CBP后6h内以清除促炎因子IL-6为主,在CBP后24h以清除抗炎因子IL-10为主,清除细胞因子多少不与脏器功能损伤的多少相关.     

内毒素对慢性HBV感染者Th1/Th2类细胞因子的影响

目的 通过研究慢性HBV感染者血浆内毒素(Endotoxin,ET)与Th1、Th2类细胞因子的关系,进而探讨其各自对慢性乙型肝炎(CHB)患者免疫功能的影响.方法 无菌收集HBV感染者和正常对照者血浆、血清,以鲎试剂法测定血浆ET水平,同时测定血清补体活性及Th1、Th2类细胞因子水平.分析ET与Th1、Th2类细胞因子的关系.结果 CHB患者IL-4与IL-10水平明显升高,IL-2、IL-12和IFN-γ水平明显降低;ET阳性组患者IL-4与IL-10水平明显高于阴性组,IL-12水平在阳性组明显低于阴性组;ET与AP50呈显著正相关.结论 CHB患者均有不同程度的Th1/Th2类细胞因子失衡,主要表现为:Th1类细胞因子减少而Th2类细胞因子增加,ET主要影响Th2类细胞因子,进而影响患者的免疫功能.     

白细胞介素-20、白细胞介素-22研究进展

白细胞介素(IL)-20、IL-22属于IL-20亚家族细胞因子,IL-20亚家族细胞因子与IL-10一同属于IL-10家族.IL-20亚家族细胞因子在结构、功能、作用的受体复合物及靶细胞上具有相似性.与IL-10家族其它成员是抑炎性因子不同,IL-20是促炎性因子,且主要在炎症早期发挥作用.IL-22在不同疾病中表现出促炎或抑炎的不同作用,其在维持黏膜屏障功能及组织内稳态中发挥了重要作用.因而研究IL-20、IL-22的细胞来源、作用的靶细胞、表达调节以及作用机制可能会使IL-20和IL-22成为治疗疾病的靶点.     

IL-22在气道变应性疾病中的作用

IL-22是一种功能复杂的细胞因子,属于IL-10细胞因子家族成员,最初被命名为IL-10相关T细胞来源诱导因子,由179个氨基酸残基组成.体内的多种活化免疫细胞可以分泌IL-22,它的受体是由IL-22R1和IL-10R2构成的异源二聚体.IL-22在固有免疫和适应性免疫中均发挥重要作用.IL-22既有抗炎作用,也有促炎作用,参与炎症性疾病和多种免疫性疾病,例如银屑病、类风湿性关节炎和炎症性肠病.另外,IL-22在消化道的感染性疾病中起到抵抗微生物的作用.因而研究IL-22在气道变应性疾病中的作用很有意义.     

白细胞介素10的生物学性质

白细胞介素10(IL-10)是近年发现的由多种免疫细胞产生并有多种生物学功能的细胞因子.它是巨噬细胞功能的有力抑制剂,但却又对B淋巴细胞发挥多种刺激作用,它还通过影响巨噬细胞功能而抑制T_H1细胞功能.IL-10的生物学性质提示了它在临床上的广泛应用前景.     

吴茱萸碱对小鼠树突状细胞分泌细胞因子的影响

目的:利用抗体芯片技术和ELISA检测吴茱萸碱(EVO)对小鼠骨髓来源树突状细胞(DC)分泌相关细胞因子的影响,研究EVO的生物学调节功能。方法:体外诱导培养未成熟DC细胞(iDC),经LPS和EVO处理后,通过混合淋巴反应检测DC诱导异源T细胞的应答能力,ELISA检测上清中IL-12p40、IL-12p70和IL-10,小鼠抗体芯片检测细胞上清中细胞因子。结果:EVO促进了iDC和成熟DC(mDC)抗原提呈功能(P0.05),对iDC、mDC的细胞因子IL-10、IL-12分泌功能无影响(P0.05),另外EVO处理iDC后上调大于2倍的细胞因子有7个(VEGF、DPPIV/CD26、IGF-Ⅰ、IL-17BR、MDC、Pro-MMP-9、Eotaxin-2),处理mDC后上调大于2倍的细胞因子有2个(Eotaxin-2、IL-13)。结论:EVO处理mDC和iDC后,细胞因子的分泌功能发生了明显改变,这些细胞因子影响着DC的抗原摄取、迁移、抗原提呈,为进一步寻找药物靶点提供了线索。     

连续性静脉-静脉血液滤过透析治疗对重症肾综合征出血热单核细胞免疫功能的影响

目的 研究连续性静脉-静脉血液滤过透析(CVVHD)治疗重症肾综合征出血热少尿期过程中对单核细胞免疫功能的影响.方法 24例重症肾综合征出血热均采用CVVHD治疗,每次治疗12 h,在治疗前及治疗后0、48、72 h,各取肝素抗凝血15 mL,分离单核细胞,用脂多糖(LPS)质量浓度10 mg/L(10 μg/mL)刺激12 h,酶联免疫吸附分析(ELISA)测定其分泌的细胞因子水平(TNF-α、IL-6、IL-10);测定单核细胞人类白细胞DR抗原(HLA-DR)的表达情况,判断其抗原呈递功能(流式细胞仪),同时观察血浆各种细胞因子水平的变化.12例健康志愿者作为正常对照组,其中男性7例,女性5例,年龄21 ～ 65岁,平均年龄42岁.结果 单核细胞分泌功能:CVVHD治疗前,重症肾综合征出血热病人单核细胞分泌功能升高,CVVHD治疗后,单核细胞分泌TNF-α、IL-6、IL-10减少.单核细胞抗原呈递功能:与正常人相比较,重症肾综合征出血热病人抗原呈递功能下降,CVVHD治疗后单核细胞抗原呈递功能明显改善.应用CVVHD治疗后血清细胞因子TNF-α、IL-6、IL-10水平明显下降.结论 应用CVVHD治疗可明显改善重症肾综合征出血热的免疫功能紊乱,可部分清除血清细胞因子TNF-α、IL-6、IL-10.接受CVVHD治疗的时间及其间隔时间是影响治疗结果的重要因素,治疗越早,治疗效果越好.     

白细胞介素-10检测及其临床意义

白细胞介素-10(简称白介素-10,interleukin-10,IL-10)是具有多种生物功能的细胞因子,它与机体自身免疫疾病、感染性疾病和肿瘤等有着密切关系.IL-10主要由单核细胞,巨噬细胞,肥大细胞,T、B淋巴细胞和激活的角质细胞产生.人的IL-10是一种单肽链的,由160个氨基酸组成的酸性蛋白,分子量为18.7kD(不包括N端18个氨基酸构成的信号肽序列),等电点为8.1,通常为二聚体(39kD).人IL-10和鼠IL-10核苷酸序列同源性达81%,氨基酸序列同源性达73%.人IL-10对人细胞和小鼠细胞均有作用,小鼠IL-10只对鼠细胞有作用,而对人细胞无作用.     

自身免疫性疾病的细胞因子调节疗法

自身免疫性疾病是一类由细胞因子、自身抗体及其联合介导的免疫性疾病.细胞因子具有双重效应,既可抵御和治疗某些疾病,也可导致和促进某些疾病的发生.因此,CK调节疗法有补充/添加疗法和阻断/拮抗疗法两类.细胞因子调节疗法包括给予抑制性细胞因子、IL-4、IL-10、IL-13和TGF-β等;投给可溶性细胞因子受体,受体的阻断剂如IL-1受体拮抗物(IL-1ra)、抗细胞因子抗体等.CK调节疗法能阻断或干扰AID的发展.细胞因子调节疗法是自身免疫性疾病的一种可靠的治疗方法.     

Th2类细胞因子与乙肝病毒相关性肝病的关系

目的:探讨慢性肝病患者血清中Th2类细胞因子IL-4、IL-6和IL-10的表达水平及临床意义.方法:以ELISA法检测肝病患者(57例)和正常对照(25例)血清IL-4、IL-6和IL-10的水平.结果:肝病患者血清中IL-4和IL-6的表达水平均明显高于正常人(肝病患者vs正常对照,IL-4,t=3.19,P<0.01;肝病患者vs正常对照,IL-6,t=3.26.P<0.01;),但肝病患者各组间细胞因子水平无统计学意义(P>0.05).肝病患者和正常人的IL-10水平均低,亦无统计学意义.结论:慢性乙肝病毒相关性肝病患者血清IL-4和IL-6水平对判断病情程度及预后有重要意义.     

Is the IL-10 Promoter Polymorphism at Position -592 Associated with Immune System-Related Diseases?

Immune responses are the main causes of immune system-related diseases such as hypersensitivities and autoimmunity. It has also been established that cytokines play key roles in the regulation of immune responses which have been shown to be important in the pathogenesis of the diseases. IL-10, the main anti-inflammatory cytokine, is produced by several immune cells such as T regulatory and Th2 lymphocytes, activated macrophages, B regulatory lymphocytes as well as other cell types. It plays a key role in the regulation of immune responses after microbe elimination (homeostasis) and against self-antigens to prevent hypersensitivity and autoimmune diseases, respectively. Studies showed that a single nucleotide polymorphism (SNP) at the -592 position of IL-10 is associated with its regulation of expression. This review addresses the recent information regarding the association of the polymorphism at position -592 of IL-10 with immune-related diseases including type 2 diabetes with and without nephropathy, multiple sclerosis, and asthma with an emphasize on Iranian patients.     

白细胞介素-35免疫调节功能研究进展

白细胞介素(IL)-35是由调节性T细胞(Tregs)分泌的具有抗炎和免疫抑制作用的细胞因子.它属于IL-12家族一员,表现出特有的生物学功能,在多种免疫相关性疾病的发病中发挥着重要作用.因而IL-35的免疫调节功能及其与相关疾病关系的研究已成为热点,为临床上免疫疾病治疗提供了新思路.     

Polymorphisms of IL-1B, IL-1RN, IL-2, IL-4, IL-6, IL-10, and IFN-gamma genes in the Korean population

Cytokines play a crucial role in regulating the immune and inflammatory responses. The collective influence of several cytokines can regulate immune responses as complex as those underlying allograft rejections or autoimmune diseases. Polymorphisms in the regulatory regions of the cytokine genes may influence their expression. Therefore, the polymorphisms of cytokine genes are potentially important as genetic predictors of the disease susceptibility or clinical outcome. In 311 unrelated healthy Korean individuals, we investigated the polymorphisms of cytokine genes (interleukin-1 [IL-1], IL-2, IL-4, IL-6, IL-10, and interferon-gamma [IFN-gamma]), which had been previously reported to be associated with a number of immune diseases, transplant complications, and direct or indirect influences on the level of expression and production. And we also compared the results to those published for other populations. The genotype distributions were consistent with the assumption of the Hardy-Weinberg equilibrium, with the exceptions of IL-1B +3954 and IL-6-174 polymorphisms. The polymorphisms examined in this study were almost similar to that observed in Asian populations. There were significant differences of the polymorphisms, except for IL-4 receptor alpha +1902, between Korean and other populations. Comparing the alleles associated with higher level of expression and production, IL-1B +3954*T, IL-2-330*G, and IL-4-590*T alleles were significantly higher, and IL-1RN*A2, IL-10-1082*G, and IFN-gamma*2 alleles were lower in Koreans than other populations. Especially in IL-6 promoter -174 polymorphism, we found only the G allele associated with higher plasma IL-6 levels. In haplotype analysis of IL-10 promoter polymorphisms, the GCC haplotype, associated with higher expression of IL-10, was significantly lower in Koreans. These results may be helpful for understanding transplant-related complications, immune or autoimmune diseases, and malignant diseases in the Korean population.     

Identification and characterization of a human IL-10 receptor antagonist

Interleukin-10 (IL-10) is an anti-inflammatory cytokine that works through IL-10 receptor alpha subunit- and suppresses immune responses in many infectious diseases such as leishmaniasis as well as in cancer. Therefore, in order to restore the host-protective immune responses in such diseases, an antagonist to this cytokine is a pressing need. Herein, using phage peptide library display, we have identified a dodecameric peptide that functions as an antagonist to human IL-10 receptor in an IL-10-induced STAT3 phosphorylation assay. The peptide antagonist’s ability to restore anti-leishmanial function in CD40-activated macrophages was also tested. We observed that the peptide reduced IL-10-induced STAT-3 phosphorylation and enhanced CD40-activated leishmanial functions in macrophages.     

Interleukin-10: new perspectives on an old cytokine

Summary: Interleukin-10 (IL-10) has long been recognized to have potent and broad-spectrum anti-inflammatory activity, which has been unequivocally established in various models of infection, inflammation, and even in cancer. However, because of the marginal successes of the initial clinical trials using recombinant IL-10, some of the interest in this cytokine as an anti-inflammatory therapeutic has diminished. New work showing IL-10 production from regulatory T cells and even T-helper 1 T cells has reinvigorated the field and revealed the power of this cytokine to influence immune responses. Furthermore, new preclinical studies suggest that combination therapies, using antibodies to IL-10 along with chemotherapy, can be effective in treating bacterial, viral, or neoplastic diseases. Studies to understand IL-10 gene expression in the various cell types may lead to new therapeutics to enhance or inhibit IL-10 production. In this review, we summarize what is known about the regulation of IL-10 gene expression by various immune cells. We speculate on the promise that this cytokine holds to influence immune responses and mitigate immune pathologies.     

Simultaneous detection of 15 human cytokines in a single sample of stimulated peripheral blood mononuclear cells

Cytokines secreted by cells of the immune system can alter the behavior and properties of immune or other cells. At a site of inflammation, sets of cytokines interact with immune cells, and their combined effect is often more important than the function of one isolated component. Conventional techniques, such as enzyme-linked immunosorbent assays, generally require large quantities of cells to characterize a complete cytokine profile of activated lymphocytes. The Bio-Plex system from Bio-Rad Laboratories combines the principle of a sandwich immunoassay with the Luminex fluorescent-bead-based technology. We developed a multiplex cytokine assay to detect different cytokines simultaneously in culture supernatant of human peripheral blood mononuclear cells stimulated with antigen and with mitogen. Fifteen human cytokines (interleukin 1alpha [IL-1alpha], IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-15, IL-17, IL-18, gamma interferon, and tumor necrosis factor alpha) were validated with a panel of healthy individuals, rheumatoid arthritis patients, and juvenile idiopathic arthritis patients. Comparing the multiplex assay with a regular enzyme-linked immunosorbent assay technique with this donor panel resulted in correlation coefficients for all cytokines ranging from 0.75 to 0.99. Intra-assay variance proved to be less then 10%, whereas interassay variability ranged between 10 and 22%. This multiplex system proved to be a powerful tool in the quantitation of cytokines. It will provide a more complete picture in differences between activated lymphocyte cytokine profiles from healthy individuals and those from patients with chronic inflammatory diseases.     

Significant Roles Played by IL-10 in Chlamydia Infections

Chlamydia species are obligate intracellular parasites which cause usually asymptomatic genital tract infections and also are associated with several complications. Previous studies demonstrated that immune responses to Chlamydia species are different and the diseases will be limited to some cases. Additionally, Chlamydia species are able to modulate immune responses via regulating expression of some immune system molecules including cytokines. IL-10, as the main anti-inflammatory cytokine, plays important roles in the induction of immune-tolerance against self-antigen and also immune-homeostasis after microbe elimination. Furthermore, it has been documented that ectopic expression of IL-10 is associated with several chronic infectious diseases. Therefore, it can be hypothesized that changes in the regulation of this cytokine can be associated with infection with several species of Chlamydia and their associated complications. This review collected the recent information regarding the association and relationship of IL-10 with Chlamydia infections. Another aim of this review article is to address recent data regarding the association of genetic variations (polymorphisms) of IL-10 and Chlamydia infections.     

Simultaneous Detection of 15 Human Cytokines in a Single Sample of Stimulated Peripheral Blood Mononuclear Cells

Cytokines secreted by cells of the immune system can alter the behavior and properties of immune or other cells. At a site of inflammation, sets of cytokines interact with immune cells, and their combined effect is often more important than the function of one isolated component. Conventional techniques, such as enzyme-linked immunosorbent assays, generally require large quantities of cells to characterize a complete cytokine profile of activated lymphocytes. The Bio-Plex system from Bio-Rad Laboratories combines the principle of a sandwich immunoassay with the Luminex fluorescent-bead-based technology. We developed a multiplex cytokine assay to detect different cytokines simultaneously in culture supernatant of human peripheral blood mononuclear cells stimulated with antigen and with mitogen. Fifteen human cytokines (interleukin 1α [IL-1α], IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-15, IL-17, IL-18, gamma interferon, and tumor necrosis factor alpha) were validated with a panel of healthy individuals, rheumatoid arthritis patients, and juvenile idiopathic arthritis patients. Comparing the multiplex assay with a regular enzyme-linked immunosorbent assay technique with this donor panel resulted in correlation coefficients for all cytokines ranging from 0.75 to 0.99. Intra-assay variance proved to be less then 10%, whereas interassay variability ranged between 10 and 22%. This multiplex system proved to be a powerful tool in the quantitation of cytokines. It will provide a more complete picture in differences between activated lymphocyte cytokine profiles from healthy individuals and those from patients with chronic inflammatory diseases.     

IL-10-Producing Lymphocytes in Inflammatory Disease

IL-10 is an anti-inflammatory cytokine that plays a significant role in controlling inflammation and modulating adaptive immune responses that cause tissue damage. IL-10-producing lymphocytes contribute to the delicate balance between inflammation and immunoregulation, and are thus regarded as a kind of “regulatory cells.” Dysregulation of these cells is linked with susceptibility to numerous inflammatory diseases. In this review, we summarized what is known about the regulatory effects of IL-10 produced by lymphocytes, including T cells, B cells and natural killer cells, in inflammatory diseases. We hope to augment immune responses or prevent immunopathology through making some small changes in the levels of IL-10 produced by lymphocytes, or in the cellular location where it is produced.