Cao Q, Batey R, Pang G, Russell A, Clancy R
Department of Gastroenterology, John Hunter Hospital, New South Wales, Australia.
Immunol Cell Biol. 1998 Dec;76(6):542-9. doi: 10.1046/j.1440-1711.1998.00779.x.
The relationship between the development of acute hepatitis and the production of TNF-alpha IFN-gamma and IL-6 by liver-associated T lymphocytes following intravenous injection of concanavalin A (Con A) was studied in rats. Following a single injection of Con A, there was a dose and time-dependent correlation in the serum levels of serum alanine aminotransferase (ALT), IL-6, IFN-gamma and TNF-alpha. These increases correlated with an increase in the numbers of CD4+, CD8+ and CD25+ T cells in blood and CD4+ and CD25+ T cells in the liver perfusate, but not with CD8+ T cells in liver perfusate. Increased levels of IL-6, IFN-gamma and TNF-alpha were constitutively produced by liver-associated CD4+ T cells when cultured. In Con A-stimulated cultures, liver-associated CD4+ T cells secreted increasing levels of TNF-alpha in a time-dependent manner following Con A injection, but TNF-alpha production by peripheral blood lymphocytes was transient with peak levels detected at 1 h which then declined over 24 h. Histological examination of the liver revealed fatty change, hepatocyte degeneration and necrosis, with an associated cell infiltrate of neutrophils and CD4+ T cells both in the portal areas and around the central veins. These results support the hypothesis that Con A-induced liver damage is mediated by CD4+ T cells acting within the liver, at least in part through the secretion of TNF-alpha, IFN-gamma and IL-6.
在大鼠中研究了静脉注射刀豆蛋白A（Con A）后急性肝炎的发展与肝脏相关T淋巴细胞产生肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）和白细胞介素-6（IL-6）之间的关系。单次注射Con A后，血清丙氨酸氨基转移酶（ALT）、IL-6、IFN-γ和TNF-α的血清水平存在剂量和时间依赖性相关性。这些升高与血液中CD4 +、CD8 +和CD25 + T细胞以及肝脏灌流液中CD4 +和CD25 + T细胞数量的增加相关，但与肝脏灌流液中的CD8 + T细胞无关。培养时，肝脏相关的CD4 + T细胞组成性产生升高水平的IL-6、IFN-γ和TNF-α。在Con A刺激的培养物中，肝脏相关的CD4 + T细胞在Con A注射后以时间依赖性方式分泌增加水平的TNF-α，但外周血淋巴细胞产生的TNF-α是短暂的，在1小时时检测到峰值水平，然后在24小时内下降。肝脏组织学检查显示脂肪变性、肝细胞变性和坏死，在门静脉区和中央静脉周围伴有中性粒细胞和CD4 + T细胞的细胞浸润。这些结果支持以下假设：Con A诱导的肝损伤至少部分是由在肝脏内起作用的CD4 + T细胞介导的，通过分泌TNF-α、IFN-γ和IL-6来实现。
