Shirin H, Bruck R, Aeed H, Hershkoviz R, Lider O, Kenet G, Avni Y, Halpern Z
Department of Gastroenterology, E. Wolfson Medical Center, Holon, Israel.
Liver. 1997 Dec;17(6):275-80. doi: 10.1111/j.1600-0676.1997.tb01032.x.
Concanavalin A (ConA) activates T lymphocytes and causes T-cell mediated hepatic injury in mice. The intravenous administration of human immunoglobulins has beneficial effects in T-cell mediated diseases such as experimental autoimmune encephalomyelitis and adjuvant arthritis. In the present study, we examined the effects of intravenous immunoglobulins in a mouse model of T-cell mediated, acute liver injury induced by concanavalin A. Balb/c mice were inoculated with 12 mg/kg concanavalin A with or without intravenous immunoglobulins at doses of 0.4, 0.6, 0.8 g/kg body wt. The serum levels of liver enzymes, tumor necrosis factor-alpha, interferon-gamma and interleukin-6 were assayed 2, 6 and 24 h after concanavalin A administration. Intravenous immunoglobulins did not prevent concanavalin A-induced hepatitis, as manifested by elevation of serum aminotransferases and histopathological evaluation. The serum levels of tumor necrosis factor-alpha in mice pretreated with immunoglobulins, measured 2 h after ConA treatment were reduced, while interferon-gamma levels measured 6 h after ConA inoculation were 5-fold higher than control levels. There was no effect of intravenous immunoglobulins on the release of interleukin 6. In conclusion, these results indicate that intravenous immunoglobulin is not effective in preventing T-cell mediated concanavalin A-induced hepatitis. The increased secretion of interferon-gamma and the incomplete suppression of tumor necrosis factor-alpha release may explain the lack of efficacy of intravenous immunoglobulin in this experimental model.
伴刀豆球蛋白A（ConA）可激活T淋巴细胞，并在小鼠中引发T细胞介导的肝损伤。静脉注射人免疫球蛋白对T细胞介导的疾病如实验性自身免疫性脑脊髓炎和佐剂性关节炎具有有益作用。在本研究中，我们检测了静脉注射免疫球蛋白在伴刀豆球蛋白A诱导的T细胞介导的急性肝损伤小鼠模型中的作用。将Balb/c小鼠接种12 mg/kg伴刀豆球蛋白A，同时或不同时静脉注射剂量为0.4、0.6、0.8 g/kg体重的免疫球蛋白。在注射伴刀豆球蛋白A后2、6和24小时检测血清肝酶、肿瘤坏死因子-α、干扰素-γ和白细胞介素-6水平。静脉注射免疫球蛋白并不能预防伴刀豆球蛋白A诱导的肝炎，血清转氨酶升高和组织病理学评估表明了这一点。在ConA治疗后2小时测量，用免疫球蛋白预处理的小鼠中肿瘤坏死因子-α的血清水平降低，而在接种ConA后6小时测量的干扰素-γ水平比对照水平高5倍。静脉注射免疫球蛋白对白细胞介素6的释放没有影响。总之，这些结果表明静脉注射免疫球蛋白在预防T细胞介导的伴刀豆球蛋白A诱导的肝炎方面无效。干扰素-γ分泌增加以及肿瘤坏死因子-α释放未被完全抑制可能解释了静脉注射免疫球蛋白在该实验模型中缺乏疗效的原因。
