来氟米特对佐剂性关节炎大鼠腹腔巨噬细胞IL—1，IL—6和TNF—α产生的动态影响

目的:探讨来氟米特(leflunomide,LEF)对佐剂性关节炎大鼠腹腔巨噬细胞IL-1,IL-6和 TNF-α分泌的影响及其抗炎、抗类风湿的可能作用机制.方法:大鼠足跖皮下注射Freund完全佐剂诱导关节炎模型;LEF灌胃后分次获取腹腔巨噬细胞,其培养上清液中IL-1,IL-6和TNF-α活性采用ELISA法或生物法测定.结果:佐剂性关节炎大鼠腹腔巨噬细胞IL-1,IL-6和TNF-α分泌较正常对照组明显升高;LEF对由 LPS诱导产生的 IL-1和 TNF-α有明显的抑制作用,作用产生快;LEF(10,25 mg/kg)在应用21天后对IL-6的分泌也有明显抑制作用.结论:来氟米特具有抑制佐剂性关节炎大鼠腹腔巨噬细胞 IL-1,IL-6和 TNF-α分泌水平的作用.     

橙皮苷对大鼠佐剂性关节炎的治疗作用及机制

目的研究橙皮苷(hesperidin,HDN)对佐剂性关节炎(AA)大鼠的治疗作用及部分机制。方法用弗氏完全佐剂(FCA)诱导大鼠AA模型;足容积法测量继发侧足肿胀度;MTT法检测刀豆蛋白(ConA)和脂多糖(LPS)诱导的脾淋巴细胞增殖反应;放免法测定脾淋巴细胞产生IL-2的水平以及腹腔巨噬细胞(PMΦ)IL-1,IL-6和TNF-α的水平;酶联免疫吸附测定法(ELISA)测定PMΦ产生IL-10的水平。结果致炎后d12,大鼠继发性关节炎出现,同时灌胃给予不同剂量的HDN(40、80、160mg·kg-1),连续12d,从致炎后d20开始,HDN(80、160mg·kg-1)对AA大鼠继发性炎症有明显抑制作用;HDN各剂量可不同程度地纠正AA大鼠低下的脾淋巴细胞增殖反应和脾细胞IL-2的产生,降低AA大鼠PMΦ产生过高的IL-1,IL-6和TNF-α,同时上调AA大鼠PMΦ低下的IL-10水平。结论HDN对AA大鼠继发性炎症具有治疗作用,其作用机制可能与调节机体异常的免疫功能和维持细胞因子网络平衡有关。     

白细胞介素1受体拮抗剂对佐剂性关节炎大鼠免疫功能的影响

采用大鼠佐剂性关节炎模型，在致炎后ｄ１８取出关节炎大鼠脾脏和腹腔渗出液，制备脾细胞和腹腔巨噬细胞悬液，并运用３Ｈ－ＴｄＲ参入法等免疫学方法观察白细胞介素１受体拮抗剂（ＩＬ－１ｒａ）对佐剂性关节炎大鼠的淋巴细胞增殖功能、ＩＬ－２和ＩＬ－１产生的影响。结果表明，ＩＬ－１ｒａ（１～３２μｇ·Ｌ－１）在体外能明显抑制大鼠腹腔巨噬细胞产生ＩＬ－１，促进脾淋巴细胞增殖及ＩＬ－２的产生。可能与其作用于白细胞介素１受体有关。     

商陆皂甙甲抑制小鼠巨噬细胞和抗体生成

商陆皂甙甲(EsA)体外在0.01～10μmol·L^-1范围内,对小鼠腹腔巨噬细胞吞噬中性红和LPS诱导的巨噬细胞合成及释放白介素1都呈明显的抑制作用。体内给药2.5～5mg·kg^-1可显著减少绵羊红细胞致敏的小鼠血清溶血素的含量。提示EsA的抗炎作用可能主要通过抑制巨噬细胞的吞噬和分泌功能。EsA间接作用于B细胞,抑制抗体生成。     

低剂量白藜芦醇增强小鼠免疫反应

目的:研究低剂量白藜芦醇的免疫调节作用.方法:用ConA和Sac分别刺激T淋巴细胞和抗原细胞并诱导细胞因子产生;[~3H]-胸腺嘧啶核苷掺入法检测淋巴细胞增殖;ELISA法检测IL-2,IL-12,IL-10和IFN-γ;用DNFB诱导小鼠迟发型超敏反应(DTH),小鼠耳肿胀作为DTH反应指标;流式细胞仪检测小鼠脾淋巴细胞亚群的变化.结果:白藜芦醇(0.75-6μmol/L)剂量依赖性地促进小鼠T淋巴细胞的增殖和IL-2的产生;白藜芦醇还剂量依赖性地促进脾脏淋巴细胞IFN-γ和IL-12的生成,同时抑制IL-10的产生;白藜芦醇(4 mg/kg)灌胃给药能对抗乙醇(16％,w/v)对小鼠DTH反应的抑制作用;白藜芦醇对脾脏淋巴细胞亚群无明显改变,但能逆转乙醇对脾淋巴细胞中巨噬细胞数量和 MHC-II分子表达的下调作用.结论:低剂量白藜芦醇能促进小鼠细胞介导的免疫反应,促进Th1细胞因子产生及影响巨噬细胞功能是其可能的机制.     

翁布总黄酮对佐剂性关节炎大鼠的免疫调节机制

目的研究翁布总黄酮对佐剂性关节炎(AA)大鼠的免疫调节机制。方法用弗氏完全佐剂(FCA)诱导大鼠AA模型。足容积法测量继发侧足肿胀度,观察该药对AA大鼠免疫器官的影响,MTT法检测ConA诱导的小鼠脾淋巴细胞增殖转化,中性红实验测定小鼠腹腔巨噬细胞吞噬功能,酶联免疫吸附测定法(ELISA)测定腹腔巨噬细胞产生IL-2和TNF-α的水平。结果致炎后d 12,大鼠继发性关节炎出现,同时灌胃给予不同剂量的翁布总黄酮及吲哚美辛,连续两周。从d 24起,翁布总黄酮(1.0、1.5 g.kg-1)对AA大鼠继发性炎症反应有明显的治疗作用。翁布总黄酮各剂量组可不同程度降低AA大鼠胸腺指数和TNF-α含量,提高淋巴细胞增殖反应、腹腔巨噬细胞吞噬功能和IL-2的含量。结论翁布总黄酮对AA大鼠继发性炎症有治疗作用,其作用机制可能与其改善AA大鼠异常的细胞免疫功能有关。     

山香圆总黄酮体外对大鼠佐剂性关节炎免疫功能的影响

目的观察山香圆总黄酮(totalflavonoidsofturpiniaargutaseen,TFS)体外对佐剂性关节炎(adjuvantarthritis,AA)大鼠免疫功能的影响。方法选择健康♂SD大鼠,采用弗氏完全佐剂(freundscompleteadjuvant,FCA)诱导AA大鼠模型:将同一批号的的卡介苗80℃水浴1h灭活,用灭菌液体石蜡配成10g·L-1的乳剂。d28处死大鼠,取AA大鼠的免疫细胞(脾细胞和腹腔巨噬细胞)体外给药培养并检测一些免疫指标:细胞增殖法检测ConA、LPS诱导的大鼠脾淋巴细胞增殖反应及IL-1、IL-2的分泌水平;放免法检测PGE2水平。结果与正常组相比,AA大鼠ConA、LPS诱导的脾淋巴细胞增殖功能低下,脾淋巴细胞产生的IL-2活性下降,LPS诱导的大鼠腹腔巨噬细胞产生的IL-1、PGE2水平明显升高。TFS(10-8~10-4)mg·L-1可纠正AA大鼠低下的脾淋巴细胞增殖反应和脾细胞IL-2的产生,降低AA大鼠腹腔巨噬细胞产生过高的IL-1和PGE2。结论山香圆总黄酮对AA大鼠的异常免疫功能具有调节作用。     

雷公藤红素对IL—1和IL—2活性及PGE2释放的抑制作用

雷公藤红素0.1～1.0μg/ml在试管内能降低LPS诱导的小鼠腹腔巨噬细胞外和细胞内白细胞介素-1(IL-1)的活性,也能抑制ConA诱导的小鼠脾细胞产生白细胞介素-2(IL-2).动态观察表明,雷公藤红素经预处理8h和3h后已能分别抑制IL-1和IL-2的产生。此外,雷公藤红素能降低A23187刺激家兔滑膜细胞释放前列腺素E_2(PGE_2)。     

木瓜苷对大鼠佐剂性关节炎的治疗作用

目的　研究木瓜苷对佐剂性关节炎 (AA)大鼠的治疗作用及部分机制。方法　大鼠足跖皮内注射弗氏完全佐剂诱发大鼠AA模型 ;足容积法测量继发侧足肿胀度 ,进行疼痛评分和多发性关节炎评分 ,MTT法检测胸腺T淋巴细胞和脾脏B淋巴细胞的增殖反应以及腹腔巨噬细胞产生IL 1水平 ,放射性免疫法测定腹腔巨噬细胞产生TNFα 和PGE2含量。结果　大鼠免疫后d 17开始分别灌胃木瓜苷 30、6 0、12 0mg·kg-1和阿克他利 6 0mg·kg-1对照药 ,连续给药 8d。木瓜苷 6 0、12 0mg·kg-1于d 2 1、d 2 4降低AA大鼠继发侧关节肿胀度、关节疼痛评分、多发性关节炎指数 ;木瓜苷 12 0mg·kg-1恢复AA大鼠胸腺T淋巴细胞增殖能力 ;木瓜苷各剂量还可不同程度抑制AA大鼠腹腔巨噬细胞产生IL 1、TNFα 和PGE2 。结论　木瓜苷可减轻AA大鼠关节肿胀、疼痛和多发性关节炎程度 ;该作用可能与调节T淋巴细胞的功能 ,抑制腹腔巨噬细胞过度分泌炎性细胞因子有关     

松果体对正常及佐剂性关节炎大鼠免疫细胞的影响

采用松果体切除（ＰＸ）及腹腔注射外源性褪黑素（ＭＴ）的方法，观察松果体对正常及佐剂性关节炎（ＡＡ）大鼠免疫细胞的影响。结果发现，ＰＸ后，ＣｏｎＡ及ＬＰＳ诱导的淋巴细胞增殖反应在正常及ＡＡ大鼠明显降低；正常大鼠ＬＰＳ诱导的腹腔巨噬细胞产生的白细胞介素Ｉ（ＩＬ－１）减少，而ＡＡ大鼠的ＩＬ－１明显增加。ＭＴ（１０μｇ·ｋｇ－１）作用则与此相反，并能使ＰＸ引起的免疫指标的改变恢复正常。上述结果表明；松果体对免细胞的功能有调节作用。     

The immunomodulatory effect(s) of lead and cadmium on the cells of immune system in vitro.

A number of studies documented that the heavy metals are not only toxic for the organisms but they may modulate immune responses. The immunomodulatory activity was proved in several in vivo and in vitro model systems. In the current study, immunomodulatory activities of lead and cadmium are presented. The viability of both lymphocytes and macrophages was affected by heavy metals in a dose- and time-dependent manner. In the case of lead, the depression of N-oxide production closely correlated with increased blast transformation of spleen cells induced by concanavalin A (ConA). On the contrary, cadmium suppressed the production of N-oxides but stimulated significantly the proliferation of spleen cells. The production of cytokines by lymphocytes and macrophages was dependent on the in vitro model used. Generally, the treatment of macrophages with lead results in disregulation of the production of proinflammatory cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin 1alpha (IL-1alpha) and interleukin 6 (IL-6)] and preferential production of Th1 type of cytokines (IFN-gamma and IL-2). Cadmium seemed to trigger the Th2 cytokine regulatory pathway [interleukin 4 (IL-4), interleukin 10 (IL-10)]. The results suggest the metal-induced changes in immunoregulatory mechanism of host with potentially severe clinical consequences.     

Interleukin-1 receptor antagonist intervenes in signaling between different types of synoviocytes in rats with adjuvant arthritis

AIM: To investigate the mechanisms of interleukin-1 receptor antagonist (IL-1ra) in the treatment of adjuvant arthritis (AA). METHODS: AA was induced in rats by treatment with Freunds complete adjuvant (FCA). Rats were given an intracutaneous injection of IL-1ra (2.5, 10, 40 mg/kg, 3 times per day) from d 14 to d 21 after immunization. Synoviocyte proliferation and the activity of IL-1 were determined by using MTT assay. Tumor necrosis factor alpha (TNF-alpha) and prostaglandin E(2) (PGE(2)) concentrations were measured by radioimmunoassay. The ultrastructure of synoviocytes was observed by using a transmission electron microscope. Phosphorylation of c-Jun N-terminal kinase (JNK), extracellular regulating kinase (ERK) and p38 kinase were detected by Western blot analysis. RESULTS: IL-1ra (10 and 40 mg/kg, ic, d 14-21) modulated the secondary inflammatory reaction (P < 0.01), ultrastructure of synoviocytes and mitogen-activated protein kinase (MAPK) phosphorylation in AA rats. The administration of IL-1ra (10 and 40 mg/kg, ic, d 14-21) in AA rats significantly decreased the production of IL-1, PGE2 and TNF-alpha by macrophage-like synoviocytes (MLS) (P < 0.01). IL-1ra (2.5 mg/kg) also decreased the production of PGE2 (P < 0.01) and TNF-alpha (P < 0.05) by MLS in AA rats. The increased phosphorylation of MAPK and cell proliferation in fibroblast-like synoviocytes (FLS) stimulated by supernatants of MLS in AA rats was also inhibited by IL-1ra (10 and 40 mg/kg, ic, d 14-21). CONCLUSION: IL-1ra has anti-inflammatory effects because it modulates the ultrastructure of synoviocytes, decreases the production of pro-inflammatory mediators by MLS, and inhibits the phosphorylation of MAPK in FLS.     

Anti-inflammatory and immunomodulatory properties of 2-amino-3H-phenoxazin-3-one

Accumulating evidence suggests that nitric oxide (NO) and prostaglandin E(2) (PGE(2)) are involved in the pathogenesis of various chronic inflammatory diseases and cancer. During the course of a screening program to identify natural anti-inflammatory substances, we isolated the compound 2-amino-3H-phenoxazin-3-one (APO) from an extract of the edible brown mushroom Agaricus bisporus IMBACH. APO inhibited NO production by mouse peritoneal macrophages in response to the pro-inflammatory stimuli lipopolysaccharide (LPS) and interferon (IFN)-gamma (LPS/IFN-gamma) at low concentrations (IC(50)=1.5 microM) through reduced inducible NO synthase protein expression. PGE(2) production by LPS/IFN-gamma-stimulated macrophages was inhibited by APO at much lower concentrations (IC(50)=0.27 microM) than those required for the inhibition of NO production. Mechanistic analysis showed that APO inhibited both cyclooxygenase (COX)-1 and COX-2 enzyme activities with almost equal selectivity. Secretion of NO and the pro-inflammatory cytokine IL-6 by IFN-gamma-activated RAW264.7 cells, a murine macrophage-like cell line, was also dose-dependently reduced by APO. Furthermore, APO increased the secretion of the anti-inflammatory cytokine IL-4 by antigen-stimulated T cells and promoted the polarization of CD4(+) Th cells toward the anti-inflammatory Th2 phenotype at equimolar concentrations that inhibited NO production. Our results suggested that APO induced polarization toward the Th2 subset, at least in part through the down-regulation of IL-12 production. Thus, APO appears to have potent anti-inflammatory and immunoregulatory properties that may provide a promising therapeutic strategy for the treatment of T cell-mediated inflammatory autoimmune diseases as well as for bacteria-induced chronic-inflammatory diseases.     

Effects of brazilin on induction of immunological tolerance by sheep red blood cells in C57BL/6 female mice

Brazilin was examined for its effects on the induction of immunological tolerance. Brazilin was administered to C57BL/6 female mice for 2 consecutive days before the immunization with high dose SRBC (10⁹ cells) which can produce immunological tolerance. Delayed type hypersensitivity, IgM plaque forming cells, ConA induced IL-2 production and mitogen- or antigen-induced proliferation of lymphocytes were measured as evaluation parameters. Administration of brazilin prior to immunization could keep the DTH and IL-2 production almost optimaly immunized levels. Brazilin also inhibited the elevation of non-specific suppressor cell activity. ConA induced proliferation of splenocytes in high dose SRBC immunized mice was significantly decreased by pretreatment of brazilin. And this might be one of the reason for augmentation of DTH by brazilin. However, IgM plaque forming cells were not affected by the treatment of brazilin. These results indicate that brazilin prevents the induction of immunological tolerance caused by high dose SRBC by suppressing the elevation of suppressor cell activity and by inhibiting the decrease in IL-2 production in C57BL/6 female mice.     

枸杞子多糖对小鼠白细胞介素-2活性的增强作用(英文)

本文研究了中药枸杞子的提取物枸杞子多糖(LBP)对成年(2月龄)和老年(16月龄)小鼠脾白细胞介素-2(IL-2)活性的影响。在诱导脾细胞IL-2的培养液(脾细胞5×10~6/ml和ConA 4μg/ml)中加入LBP,所制备的含IL-2上清液使成年小鼠胸腺细胞在体外增殖活性([~3H]TdR参入法)升高。老年小鼠IL-2促进淋巴细胞增殖水平显著低于成年。LBP可使老年小鼠IL-2的这种作用显著提高,达成年水平。这些结果表明,LBP对IL-2的活性有增强作用并使老年小鼠IL-2活性得到恢复。     

商陆皂苷甲对细胞间粘附的影响商陆皂苷甲对细胞间粘附的影响

目的研究商陆皂苷甲(EsA)对细胞间粘附的影响，并观察粘附分子ICAM-1和CD18 mRNA的表达水平。方法用血细胞计数仪计数的方法考察在脂多糖（LPS）诱导下，EsA对中性粒细胞与内皮细胞间粘附的影响。用逆转录聚合酶链反应（RT-PCR）的方法测定内皮细胞ICAM-1 mRNA和中性粒细胞CD18 mRNA的表达水平。结果EsA在3～12×10^-6　μmol·L^-1能降低LPS作用下中性粒细胞与内皮细胞间高水平的粘附率，且能降低LPS诱导下内皮细胞ICAM-1 mRNA和中性粒细胞CD18 mRNA的表达。结论EsA能抑制LPS作用下中性粒细胞与内皮细胞间的粘附可能是其抗炎机制之一，降低粘附分子的表达可能是其影响细胞间粘附的重要作用机制。