Heumann D, Le Roy D, Zanetti G, Eugster H P, Ryffel B, Hahne M, Tschopp J, Glauser M P
Department of Internal Medicine, CHUV, Laussane, Switzerland.
J Inflamm. 1995;47(4):173-9.
Fas/Fas ligand and TNF/TNF receptors are involved in apoptosis. Whether both systems are involved in septic shock has not been determined so far. We investigated the role of TNF/TNFR and Fas/Fas ligand in models of endotoxemia and of speticemia in mice. Upon LPS challenge, TNF and TNFR p55 were involved in the process inducing lethality. FasL did not contribute to enhance lethality, as evidenced in gld mice, lacing FasL. Following an intraperitoneal injection of live E. coli, TNF and TNFR p55 were necessary to combat infection. Disruption of either gene was associated with enhanced lethality and failure to clear the bacteria. No effect observed in gld mice in this peritonitis model. Thus, these observations confirmed the pathogenic role of TNF/TNFR in endotoxemia and its beneficial role in local bacterial infections. In addition the data ruled out a major role for Fas/FasL in septic shock in mice.
Fas/Fas配体和TNF/TNF受体参与细胞凋亡。到目前为止，这两个系统是否都参与脓毒性休克尚未确定。我们在小鼠内毒素血症和败血症模型中研究了TNF/TNFR和Fas/Fas配体的作用。在LPS刺激后，TNF和TNFR p55参与了诱导致死性的过程。如在缺乏FasL的gld小鼠中所证明的，FasL对增强致死性没有作用。腹腔注射活大肠杆菌后，TNF和TNFR p55是对抗感染所必需的。任一基因的破坏都与致死性增强和细菌清除失败有关。在该腹膜炎模型中，gld小鼠未观察到影响。因此，这些观察结果证实了TNF/TNFR在内毒素血症中的致病作用及其在局部细菌感染中的有益作用。此外，数据排除了Fas/FasL在小鼠脓毒性休克中的主要作用。
