Production and role of interleukin-10 in concanavalin A-induced hepatitis in mice
Production and role of interleukin-10 in concanavalin A-induced hepatitis in mice
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DOI：
10.1002/hep.510250614
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发表时间：
1997-06-01
期刊：
影响因子：
13.5
通讯作者：
Deviere, J
中科院分区：
文献类型：
--
作者：
Louis, H;LeMoine, O;Deviere, J
刀豆蛋白A(ConA)诱导的实验性T细胞介导性肝炎涉及促炎细胞因子的产生。由于IL-10是一种来源于巨噬细胞和T细胞的有效抗炎细胞因子，在肝脏内产生，我们研究了IL-10在调节ConA体内注射后的肝毒性和细胞因子分泌中的作用，ConA攻击后血清中早期产生IL-10。用单抗中和内源性IL-10可增加注射刀豆蛋白A后8小时肿瘤坏死因子α(+111%)、干扰素-γ(+92%)和IL-12(+730%)的分泌，并增加肝脏毒性，通过血清丙氨酸转氨酶(ALT)测定(+174%)和组织学评估，在诱导肝炎后24小时，相反，预先应用重组IL-10可减少这些促炎细胞因子的产生(-47%，-80%和-47%)。Con A刺激后8h，IL-10可降低中性粒细胞浸润和血清ALT浓度(-74%)，提示内源性和外源性IL-10对ConA诱导的肝炎具有肝保护作用，其机制可能与抑制促炎细胞因子的产生有关，并可能与T细胞活化的肝病的治疗有关。
Experimental T-cell-mediated hepatitis induced by concanavalin A (Con A) involves the production of proinflammatory cytokines. Because interleukin (IL)-10 is a potent anti-inflammatory cytokine derived from macrophage and T cells and is produced within the liver, we investigated the role of IL-10 in modulating the hepatotoxicity and the secretion of cytokines following tit vivo injection of Con A, IL-10 is produced early in the serum after Con A challenge. Neutralization of endogenous IL-10 by monoclonal antibodies (mAbs) increases the secretion of tumor necrosis factor alpha (TNF-alpha) (+111%), interferon gamma (IFN-gamma) (+92%), and IL-12 (+730%) 8 hours after Con A injection, and increases the hepatotoxicity, assessed by serum alanine transaminase (ALT) (+174%) measurement and by histology, 24 hours after induction of hepatitis, Conversely, preadministration of recombinant IL-10 reduces the production of these proinflammatory cytokines (-47%, -80%, and -47% for TNF-alpha, IL-12, and IFN-gamma, respectively), and decreases neutrophil infiltration and ALT serum concentration (-74%) 8 hours after Con A challenge, We conclude that IL-10, either endogenously produced or exogenously added, has a hepatoprotective role in Con A-induced hepatitis, through its suppressive property on proinflammatory cytokine production, and that it might be of therapeutic relevance in human Liver diseases involving activated T cells.