湖南汉族人群IL-1O启动子和IL-1ra基因多态性与SLE相关性研究

目的:研究湖南汉族人群IL-10启动子和IL-1受体拮抗剂(IL-1ra)的基因多态性,探讨IL-10启动子和IL-1ra基因多态性与SLE疾病的关系。方法:PCR和限制性内切酶酶切分析SLE患者(n=83)和正常对照人群(n=125)IL-10启动子和IL-1ra基因多态性,对基因频率进行分析。结果:湖南汉族人群IL-1ra及IL-10启动子基因具有多态性;SLE患者IL-1RN*1等位基因的频率显著高于正常对照组(P<0.05,RR=5);SLE患者IL-10启动子区-597位*A、-824位*T和ACC亚型的基因频率高于正常对照组(P<0.001)。结论:SLE患者IL-1RN*1的基因频率、IL-10启动子区-597位和-824位的基因多态性与正常人比较有显著差异,提示以上基因可能与SLE的发病有一定相关性。     

The abnormal apoptosis of T cell subsets and possible involvement of IL-10 in systemic lupus erythematosus

To study the apoptosis of lymphocyte subpopulations in systemic lupus erythematosus (SLE) patients and the possible role of IL-10 in this apoptosis involved in the pathogenesis of SLE, three color fluorescence and flow cytometry were used to investigate the early apoptosis of lymphocyte subsets from freshly separated or cultured peripheral blood mononuclear cells (PBMCs). ELISA was employed to detect the levels of IL-10 in serum and the levels of sFas and sFasL in cultured PBMC supernatants, and the results of sFas and sFasL were confirmed by real-time PCR of Fas and FasL mRNA. The results showed that in cells from SLE patients, the apoptosis of CD3+, CD4+, and CD8+ T cells was distinctly increased, and the percentage of CD4+ cells and the CD4/CD8 ratio was significantly decreased, as compared with normal controls. The apoptosis of T lymphocytes cultured with SLE serum was markedly higher than that of cells cultured with control's serum. Blockade of interleukin-10 (IL-10) activation by an anti-IL-10 antibody reduced the SLE serum induced apoptosis of CD4+ and CD8+ T cells. The levels of sFas and sFasL in the culture supernatant and Fas and FasL mRNA expressions in cultured cells were significantly higher in the SLE serum-cultured groups, but decreased evidently in the presence of the anti-IL-10 antibody. Above findings suggested that SLE cells showed abnormally high apoptosis of T lymphocytes, especially of the CD4+ subpopulation, resulting in a decreased CD4/CD8 ratio. The high percentage of apoptotic T cells in SLE patients may be related to the high levels of IL-10 in SLE serum, as IL-10 may induce the abnormally activated T cells to trigger apoptosis via the Fas-FasL pathway.     

三氧化二砷对系统性红斑狼疮患者外周血淋巴细胞凋亡和IL-10分泌的影响

目的观察不同浓度三氧化二砷（As2O3）对活动期系统性红斑狼疮（SLE）患者外周血淋巴细胞凋亡及白介素10（IL-10）分泌的影响。方法收集15例未曾用过激素及免疫抑制剂治疗并排除其它类型的自身免疫性疾病及感染性疾病的初诊SLE患者和同期15例健康体检者（健康对照组）的外周血,分别于不同浓度As2O3干预培养后12h和24h采用VnnexinV＼PI染色定量分析外周血淋巴细胞凋亡率,采用酶联免疫吸附法（ELISA）检测培养上清液中IL-10的含量。结果SLE组患者和健康对照组在不同As2O3浓度下12h和24h的凋亡率均增加（P〈0．05）;不同浓度As2O3诱导SLE患者在12h和24h淋巴细胞凋亡率明显高于健康对照组（P〈0．05）;且随As2O3干预浓度的增加,两组外周血淋巴细胞凋亡率均增加（P〈0．05）。SLE组患者外周血淋巴细胞在体外培养后分泌IL-10水平明显高于健康对照组（P〈0．05）,且As2O3能显著抑制其分泌,As2O3对健康对照组无影响（P〉0．05）。结论As2O3能诱导外周血淋巴细胞凋亡,并且具有时间和浓度依赖性,提示As2O3通过引起淋巴细胞凋亡发挥治疗作用;As2O3抑制SLE患者外周血淋巴细胞分泌IL-10可能是其发挥治疗作用的重要机制之一。     

白细胞介素-10、白细胞介素-6对慢性肺源性心脏病预后评价的临床意义

目的:检测慢性肺源性心脏病患者血清白细胞介素-10和白细胞介素-6的水平,探讨细胞因子对慢性肺源性心脏病患者预后评价的临床意义。方法:将我院住院治疗的慢性肺源性心脏病患者40例,按照心功能情况分为肺源性心脏病组21例(对照组)和肺源性心脏病合并心力衰竭组19例(观察组),进行血清白介素-6、白介素-10定量检测。结果:观察组血清白介素-6水平较对照组明显升高,而白细胞介素-10却明显低于对照组(P值均<0.05)。结论:检测白细胞介素-6、白细胞介素-10的水平,可作为监测肺源性心脏病心功能恶化的预测指标。     

湖南汉族人群IL-10启动子和IL-1rα基因多态性与SLE相关性研究

目的：研究湖南汉族人群IL-10启动子和IL-1受体拮抗剂（IL-1rα）的基因多态性,探讨IL-10启动子和IL-1rα基因多态性与SLE疾病的关系。方法：PCR和限制性内切酶酶切分析SLE患者（n=83）和正常对照人群（n=125）IL-10启动子和儿-1rα基因多态性,对基因频率进行分析。结果：湖南汉族人群IL-1rα及儿．10启动子基因具有多态性;SLE患者IL-1RN ＊ 1等位基因的频率显著高于正常对照组（P〈0．05,RR=5）;SLE患者IL-10启动子区-597位女A ＊、-824位＊T和ACC亚型的基因频率高于正常对照组（P〈0．001）。结论：SLE患者IL-1RN ＊1的基因频率、IL-10启动子区-597位和-824位的基因多态性与正常人比较有显著差异,提示以上基因可能与SLE的发病有一定相关性。     

系统性红斑狼疮患者血清中IL-17 的检测及临床意义

目的:通过检测系统性红斑狼疮(SLE)患者外周血中IL-17的水平,探讨其临床意义。方法:用酶联免疫吸附法(enzymelinked immunosorbent assay,ELISA)检测61例SLE患者及30例健康人血清IL-17水平,并收集整理SLE患者的临床资料及实验室数据,分析其与临床的关系。结果:活动期SLE患者血清IL-17水平明显高于正常对照组(P<0.01),与SLE非活动组相比,差异亦有统计学意义(P<0.01)。但SLE非活动组与正常对照组间无统计学意义。结论:IL-17水平在活动期SLE患者血清中表达明显增高,且与SLEDAI评分呈正相关,提示IL-17可能参与了SLE疾病的病理过程,可能与疾病活动的关系密切。     

Potential role of melatonin in autoimmune diseases

Autoimmune diseases are a broad spectrum of disorders involved in the imbalance of T-cell subsets, in which interplay or interaction of Th1, Th17 and Tregs are most important, resulting in prolonged inflammation and subsequent tissue damage. Pathogenic Th1 and Th17 cells can secrete signature proinflammatory cytokines, including interferon (IFN)-γ and IL-17, however Tregs can suppress effector cells and dampen a wide spectrum of immune responses. Melatonin (MLT) can regulate the humoral and cellular immune responses, as well as cell proliferation and immune mediators. Treatment with MLT directly interferes with T cell differentiation, controls the balance between pathogenic and regulatory T cells and regulates inflammatory cytokine release. MLT can promote the differentiation of type 1 regulatory T cells via extracellular signal regulated kinase 1/2 (Erk1/2) and retinoic acid-related orphan receptor-α (ROR-α) and suppress the differentiation of Th17 cells via the inhibition of ROR-γt and ROR-α expression through NFIL3. Moreover, MLT inhibits NF-κB signaling pathway to reduce TNF-α and IL-1β expression, promotes Nrf2 gene and protein expression to reduce oxidative and inflammatory states and regulates Bax and Bcl-2 to reduce apoptosis; all of which alleviate the development of autoimmune diseases. Thus, MLT can serve as a potential new therapeutic target, creating opportunities for the treatment of autoimmune diseases. This review aims to highlight recent advances in the role of MLT in several autoimmune diseases with particular focus given to novel signaling pathways involved in Th17 and Tregs as well as cell proliferation and apoptosis.     

Interleukin-10 in serous ovarian carcinoma cell lines

 Interleukin-10, one of the most potent anti-inflammatory cytokines, is expressed in ovarian carcinomas in vivo. In contrast to the high levels of IL-10 in ascites and tumour tissue, the expression of this cytokine appears to be a rare event in ovarian carcinoma cell lines in vitro. Virtually nothing is known about the regulation of IL-10 expression in ovarian carcinoma cell lines. We investigated the expression of IL-10 in four cell lines originally derived from ovarian serous adenocarcinoma: OVCAR-3, SKOV-3, CAOV-3 and OAW-42. IL-10-specific mRNA was detected in OVCAR-3 and only this cell line produced IL-10 constitutively under serum-free conditions as well as in serum-containing medium. Our studies on the regulation of IL-10 secretion in OVCAR-3 revealed that (1) proinflammatory stimuli IL-1β and TNF-α, but not LPS, enhance IL-10 secretion, (2) IL-6 has no influence on the release of IL-10, (3) prostaglandin E2 influences neither the spontaneous nor the TNF-α- or IL-1β-stimulated IL-10 production and (4) interferon-γ inhibits IL-10 secretion. We conclude that only a minority of serous ovarian carcinoma cells maintain the ability to produce IL-10 in vitro. Our data on the regulation of IL-10 production in OVCAR-3 indicate that ovarian carcinoma cells share some, but not all, of the regulatory features typical for the monocytic IL-10 secretion. Received: 1 February 2001 / Accepted: 29 March 2001     

The light and dark sides of intestinal intraepithelial lymphocytes

The intraepithelial lymphocytes (IELs) that reside within the epithelium of the intestine form one of the main branches of the immune system. As IELs are located at this critical interface between the core of the body and the outside environment, they must balance protective immunity with an ability to safeguard the integrity of the epithelial barrier: failure to do so would compromise homeostasis of the organism. In this Review, we address how the unique development and functions of intestinal IELs allow them to achieve this balance.     

系统性红斑狼疮与肠道菌群关系研究进展

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种慢性进行性自身免疫疾病,可累及全身多器官。SLE的发病机制不仅与遗传易感性有关,还与环境因素有关,其中肠道菌群紊乱引起了越来越多的关注。研究表明,肠道菌群是影响自身免疫性疾病发病率的环境因素。公认的机制包括异常的微生物移位、分子拟态以及局部和全身免疫的失调。因此,肠道菌群及其代谢物影响SLE的发生发展。本文将重点探讨肠道菌群与SLE的关系,以及菌群干预作为SLE防治的新策略,为进一步研究SLE的诊断和治疗提供新的思路。     

Interleukin-10 inhibits neutrophil phagocytic and bactericidal activity

Abstract Effective host defense against bacterial invasion is characterized by the vigorous recruitment and activation of inflammatory cells, which is dependent upon the coordinated expression of both pro- and anti-inflammatory cytokines. Interleukin-10 (IL-10) is a recently described cytokine with potent anti-inflammatory properties in vivo and in vitro. In this study we investigated whether IL-10 could directly regulate the ability of neutrophils (PMN) to phagocytose and kill bacteria. Initial studies demonstrated that human recombinant IL-10 (hrIL-10) inhibited the ability of PMN to phagocytose Escherichia coli in vitro. Inhibition of phagocytosis occurred in the absence of changes in CR1 (C3b) or Fc receptor expression, as treatment of PMN with IL-10 failed to induce significant changes in FcγIIR, FcγIIIR or CR1 cell surface expression. However, incubation of PMN with IL-10 resulted in a dose-dependent decrease in CD11b (Mac-1) expression. In addition to effects on PMN phagocytosis, hrIL-10 significantly attenuated PMN microbicidal activity, as bactericidal assays revealed that co-incubation of PMN with hrIL-10 resulted in a marked decrease in killing of phagocytosed bacteria. Furthermore, IL-10 inhibited the production of superoxide from PMA-stimulated PMN, suggesting that the detrimental effects of IL-10 on PMN microbicidal activity were due, in part, to suppression of respiratory burst. In summary, our studies indicate that IL-10 inhibits PMN-dependent phagocytosis and killing of E. coli in vitro, and suggest that this cytokine may impair effective antibacterial host defense in vivo.     

Interleukin-10 and sudden infant death syndrome

Uncontrolled pro-inflammatory responses to infections or bacterial toxins have been suggested to play a role in triggering the physiological events leading to sudden infant death syndrome (SIDS). We tested the hypothesis that these uncontrolled responses might be due to interactions between the gene polymorphisms inducing low levels of IL-10 and exposure to cigarette smoke. In vitro, the IL-10 (G-1082A) polymorphism was associated with low IL-10 levels and the -1082G allele was associated with high levels. The first objective was to assess the distribution of this polymorphism among SIDS infants, parents of SIDS infants and controls, and two ethnic groups: Aboriginal Australians who have a high incidence of SIDS; and Bangladeshis who in Britain have a low incidence of SIDS compared with Europeans. The second objective was to assess effects of human recombinant IL-10 on interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) responses of human leukocytes to staphylococcal toxins implicated in SIDS. The third objective was to assess IL-10 responses to endotoxin and toxic shock syndrome toxin (TSST) from leukocytes of smokers and non-smokers in relation to the IL-10 (G-1082A) polymorphism. There were major differences in the distributions of these polymorphisms between Europeans and Bangladeshis (p=0.00) and between Europeans and Aboriginal Australians (p=0.00); however, they were similar for the Bangladeshi and Aboriginal Australian subjects. There were no significant differences in the distribution of these polymorphisms among SIDS infants or parents of SIDS infants compared to control groups. IL-10 significantly reduced IL-6 and TNF-alpha responses to TSST and staphylococcal enterotoxins A and C. At 50 ng ml(-1), IL-10 significantly increased TNF-alpha but not IL-6 responses to TSST and enterotoxin A. Although IL-10 responses to endotoxin were lower from leukocytes of smokers who were homozygous for the G allele, the differences were not significant; however, significantly lower IL-10 responses were found for smokers who were homozygous for the A allele (p=0.01) and heterozygotes (p=0.04). The pooled data found smokers had significantly lower levels of IL-10 responses to TSST, but there were no significant differences for smokers compared with non-smokers for the three genotypes. The high incidence of SIDS and serious respiratory infections among Aboriginal Australian infants and the low incidence of these conditions among Bangladeshi infants might be explained in part by our findings of differences in IL-10 responses between smokers and non-smokers. The lowest levels of IL-10 responses were observed among smokers who were homozygous for the A allele which is most prevalent among the Aboriginal Australians (83%) and Bangladeshis (84%). The major difference between the risk factors for SIDS in these two groups is the level of exposure of infants to cigarette smoke associated with maternal smoking.     

IL-10基因启动子-627位点多态性与过敏性哮喘

目的：探讨白细胞介素-10（IL-10）启动子-627C／A基因多态性和等位基因频率与过敏性哮喘血清IgE、IL-10浓度以及病情严重程度的相互关系。方法：从哮喘病人DNA文库中选择青岛地区过敏性哮喘病人518例和健康志愿者501例,采用PCR—RFLP方法对IL．10基因启动子．627位点多态性进行观察,比较两组基因型和等位基因的分布频率,同时测定血清中总IgE、IL-10浓度和肺功能检查（FEV1、FVC、FEV1／FVC）。结果：轻度和中一重度哮喘组AA、CA和CC基因型所占比例分别为38．1％、46．0％、15．9％和45．6％、46．2％和8．2％（P=0．0168,X2=8．232,df=2）。A等位基因与哮喘病轻的严重程度有明显相关性（P〈0．05）。AA基因型哮喘病人血清的IgE浓度显著升高（P〈0．01）,但其血清IL-10浓度比CC基因型携带者明显降低（P〈0．01）。结论：IL-10基因启动子-627位点多态性与过敏性哮喘的发生有一定的相关性,等位基因A是哮喘患病的风险基因,而等位基因C则是哮喘病的保护基因。     

The effects of freeze/thawing on the function and phenotype of CD4+ lymphocyte subsets in normal individuals and patients with systemic lupus erythematosus

Several studies report on lymphocyte phenotypic and functional abnormalities in Systemic Lupus Erythematosus (SLE). Freezing and thawing may alter functional and phenotypic properties of cells. We assessed the effect of the freezing/thawing process (F/T) on Th1 (CD3⁺CD4⁺CCR4⁻CXCR3⁺CCR5⁺), Th2 (CD3⁺CD4⁺CCR5⁻CXCR3⁻CCR4⁺), Th17 (CD3⁺CD4⁺CCR6⁺CD161⁺), and Treg (CD3⁺CD4⁺CD25^highCD127^-) cell cultures in healthy controls and SLE patients. F/T was associated with decreased frequency of Th2 and Th17 cells in cultures from SLE patients but not from controls. F/T was also associated with increased frequency of apoptotic cells, as measured by annexin V labeling, in all T cell subtypes analyzed, as well as increased cell proliferation, as measured by Ki-67 labeling, in all cells except Th1 from SLE patients. Thus, F/T can have differentiated effects on T lymphocyte subtypes from SLE patients and controls, and can have significant effects on cell death and proliferation. These findings should be carefully considered when designing and interpreting studies on functional and phenotypic aspects of T lymphocytes in SLE.     

IL-17 与狼疮性肾炎关系的研究新进展

系统性红斑狼疮是一种涉及多系统损害的自身免疫性疾病,其主要并发症及死亡原因之一是狼疮性肾炎。研究表明,IL-17和产IL-17细胞可以浸润肾脏,与其他细胞因子协同作用,引起肾脏局部炎症反应。拮抗IL-17的生物制剂已应用于银屑病、强制性脊柱炎等免疫介导炎症性疾病,但在系统性红斑狼疮及狼疮性肾炎的研究尚少。本文对IL-17与狼疮性肾炎的关系进行综述,探讨IL-17及其抑制剂在狼疮性肾炎治疗的作用及发展前景。     

IL-10基因启动子-627位点多态性与过敏性哮喘

目的:探讨白细胞介素-10(IL-10)启动子-627C/A基因多态性和等位基因频率与过敏性哮喘血清IgE、IL-10浓度以及病情严重程度的相互关系。方法:从哮喘病人DNA文库中选择青岛地区过敏性哮喘病人518例和健康志愿者501例,采用PCR-RFLP方法对IL-10基因启动子-627位点多态性进行观察,比较两组基因型和等位基因的分布频率,同时测定血清中总IgE、IL-10浓度和肺功能检查(FEV1、FVC、FEVl/FVC)。结果:轻度和中-重度哮喘组AA、CA和CC基因型所占比例分别为38.1%、46.0%、15.9%和45.6%、46.2%和8.2%(P=0.0168,X~2=8.232,df=2)A等位基因与哮喘病轻的严重程度有明显相关性(P<0.05)。AA基因型哮喘病人血清的IgE浓度显著升高(P<0.01),但其血清IL-10浓度比CC基因型携带者明显降低(P<0.01)。结论:IL-10基因启动子-627位点多态性与过敏性哮喘的发生有一定的相关性,等位基因A是哮喘患病的风险基因,而等位基因C则是哮喘病的保护基因。     

Interleukin-10 and interleukin-13 inhibit proinflammatory cytokine-induced ceramide production through the activation of phosphatidylinositol 3-kinase

Ceramide produced by hydrolysis of plasma membrane sphingomyelin (SM) in different cells including brain cells in response to proinflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta)] plays an important role in coordinating cellular responses to stress, growth suppression, and apoptosis. The present study underlines the importance of IL-10 and IL-13, cytokines with potent antiinflammatory properties, in inhibiting the proinflammatory cytokine (TNF-alpha and IL-1beta)-mediated degradation of SM to ceramide in rat primary astrocytes. Treatment of rat primary astrocytes with TNF-alpha or IL-1beta led to rapid degradation of SM to ceramide, whereas IL-10 and IL-13 by themselves were unable to induce the degradation of SM to ceramide. Interestingly, both IL-10 and IL-13 prevented proinflammatory cytokine-induced degradation of SM to ceramide. Both IL-10 and IL-13 caused rapid activation of phosphatidylinositol (PI) 3-kinase, and inhibition of that kinase activity by wortmannin and LY294002 potently blocked the inhibitory effect of IL-10 and IL-13 on proinflammatory cytokine-mediated induction of ceramide production. This study suggests that the inhibition of proinflammatory cytokine-mediated degradation of SM to ceramide by IL-10 and IL-13 is mediated through the activation of PI 3-kinase. As ceramide induces apoptosis and IL-10 and IL-13 inhibit the induction of ceramide production, we examined the effect of IL-10 and IL-13 on proinflammatory cytokine-mediated apoptosis. Inhibition of TNF-alpha-induced apoptosis by IL-10 and IL-13 suggests that the antiapoptotic nature of IL-10 and IL-13 is probably due to the inhibition of ceramide production.     

Salivary levels of inflammatory cytokines and their association to periodontal disease in systemic lupus erythematosus patients. A case-control study

Both Systemic Lupus Erythematosus (SLE) and periodontal disease (PD) present a similar immunological profile mainly characterized by altered cytokine levels. In this study we sought to investigate the salivary levels of inflammatory cytokines and their association with PD in SLE patients. 60 patients with SLE and 54 systemically healthy individuals underwent a full periodontal clinical examination. They were then grouped according to their periodontal status. Stimulated saliva was collected in order to evaluate the salivary levels of interferon (IFN-γ), Interleukin (IL)-10, IL-17, IL-1β, and IL-4. Systemically healthy individuals with periodontitis (group P) presented higher levels of cytokines when compared to systemically healthy individuals, with no periodontal disease (group S) (p < 0.05). Additionally, in the P group, patients presented similar levels of cytokines to those of the patients with SLE, regardless of the presence of PD (p > 0.05), for most of the analyzed cytokines. There was a positive correlation in SLE patients, including IL-1β and all periodontal clinical parameters (p < 0.05), and between IL-4 and gingival bleeding index and the presence of biofilm (p < 0.05). Thus, our results confirmed, that patients with PD showed higher salivary levels of cytokines and, in SLE patients, the increased levels of salivary cytokines were observed even in the absence of periodontitis. IL-1β and IL-4 salivary levels were also positively correlated with periodontal status indicating their potential as markers of the amount and extent of periodontal damage in patients with SLE.     

Gelsolin蛋白在类风湿性关节炎和系统性红斑狼疮的临床诊断及疾病活动度评价中的意义

目的:分析gelsolin蛋白对类风湿性关节炎(rheumatoid arthritis,RA)和系统性红斑狼疮(systemic lupus erythematosus,SLE)的临床诊断及疾病活动度评价的意义。方法:采集RA 30名和SLE 47名及健康人群50名的临床资料及血清标本,定量Western Blot法检测血清gelsolin水平。分析gelsolin蛋白与RA和SLE患者临床表现及疾病活动度的相关性。结果:RA、SLE和正常对照组之间性别、年龄、血红蛋白、血小板、血红细胞、血白细胞之间没有显著差异;RA患者出现CRP、转氨酶、RF、CCP异常的阳性率明显高于SLE患者(P0.05);而SLE患者出现白蛋白、尿蛋白、尿红细胞、尿素氮、ANA、肌酐异常增高的几率高于RA患者(P0.05)。gelsolin蛋白在SLE和RA血清中的含量均显著低于正常人(P0.05),且RA患者含量更低(P0.05)。gelsolin蛋白滴度与RA的疾病活动度无明显相关性(r=0.089,P=0.652),而与SLE的疾病活动度呈显著负相关(r=0.646,P0.05)。gelsolin蛋白正常组RA患者的转氨酶升高、CRP、RF、CCP阳性率均显著高于SLE患者(P0.05)。gelsolin蛋白降低组SLE患者的白蛋白、尿蛋白、尿红细胞、尿素氮、ANA、肌酐阳性率显著高于RA患者(P0.05)。结论:gelsolin蛋白滴度检测可作为RA和SLE临床辅助诊断手段,其滴度变化可作为SLE疾病活动度进展的预判指标。     

Interleukin-10 inhibits both production of cytokines and expression of cytokine receptors in microglia

Microglia, macrophage-like cells in the CNS, are multifunctional cells; they play an important role in removal of dead cells or their remnants by phagocytosis in the CNS degeneration and are one of important cells in the CNS cytokine network to produce and respond to a variety of cytokines. The functions of microglia are regulated by inhibitory cytokines. We have reported the expression of interleukin (IL)-10, one of the inhibitory cytokines, and its receptor in mouse microglia; therefore, IL-10 may affect microglial functions. In this study, we investigated the effects of IL-10 on purified microglia in culture. IL-10 inhibited lipopolysaccharide-induced IL-1beta and tumor necrosis factor-alpha production, lysosomal enzyme activity, and superoxide anion production in a dose-dependent manner, but did not affect granulocyte/ macrophage colony-stimulating factor-dependent proliferation of microglia. IL-10 also decreased the expression of both IL-6 receptor and lipopolysaccharide-induced IL-2 receptor but not IL-4 receptor on microglia as measured by flow cytometric analysis with an indirect immunofluorescence technique. IL-10 also decreased mRNA expression of IL-2 and IL-6 cytokine receptors. These results suggest that IL-10 is a unique and potent inhibitory factor in the CNS cytokine network involved in decreasing the expression of cytokine receptors as well as cytokine production by microglia.