Jansen P M, Eisele B, de Jong I W, Chang A, Delvos U, Taylor F B, Hack C E
Central Laboratory of the Netherlands Red Cross Blood Transfusion Services and Laboratory for Experimental and Clinical Immunology, Academic Medical Centre, University of Amsterdam, The Netherlands.
J Immunol. 1998 Jan 1;160(1):475-84.
We evaluated the effect of C1 inhibitor (C1-inh), an inhibitor of the classical pathway of complement and the contact system, on the physiologic and inflammatory response in baboons suffering from lethal Escherichia coli sepsis. Five animals pretreated with 500 U/kg C1-inh (treatment group; n = 5), followed by a 9-h continuous infusion of 200 U/kg C1-inh subsequent to bacterial challenge, were compared with five controls receiving E. coli alone. Of the treatment group, one animal survived and another lived beyond 48 h, whereas all control animals died within 27 h. In four of five treated animals, less severe pathology was observed in various target organs. C1-inh administration did not prevent the hemodynamic or hematologic changes observed upon E. coli infusion. The activation of fibrinolysis and the development of disseminated intravascular coagulation were essentially unaffected by C1-inh. However, C1-inh supplementation significantly reduced decreases in plasma levels of factor XII and prekallikrein and abrogated the systemic appearance of C4b/c, indicating substantial inhibition of activation of the contact system and the classical complement pathway, respectively. Furthermore, treated animals displayed a reduced elaboration of various cytokines including TNF, IL-10, IL-6, and IL-8. Thus, the administration of C1-inh may have a beneficial but modest effect on the clinical course and outcome of severe sepsis in nonhuman primates. We suggest that activated complement and/or contact system proteases may, at least in part, contribute to the attendant manifestations of septic shock through an augmentation of the cytokine response.
我们评估了补体经典途径和接触系统的抑制剂C1抑制剂（C1-inh）对患有致死性大肠杆菌败血症的狒狒生理和炎症反应的影响。将5只预先接受500 U/kg C1-inh治疗的动物（治疗组；n = 5），在细菌攻击后接着进行9小时200 U/kg C1-inh的持续输注，与5只仅接受大肠杆菌的对照动物进行比较。治疗组中，1只动物存活，另1只存活超过48小时，而所有对照动物在27小时内死亡。在5只接受治疗的动物中的4只，在各个靶器官中观察到的病理变化较轻。给予C1-inh并不能预防大肠杆菌输注后观察到的血流动力学或血液学变化。纤维蛋白溶解的激活和弥散性血管内凝血的发展基本上不受C1-inh的影响。然而，补充C1-inh显著减少了血浆中因子XII和前激肽释放酶水平的下降，并消除了C4b/c的全身出现，分别表明对接触系统和补体经典途径的激活有实质性抑制。此外，接受治疗的动物表现出包括TNF、IL-10、IL-6和IL-8在内的各种细胞因子的分泌减少。因此，给予C1-inh可能对非人类灵长类动物严重脓毒症的临床病程和结局有有益但适度的影响。我们认为，活化的补体和/或接触系统蛋白酶可能至少部分地通过增强细胞因子反应而导致脓毒性休克的伴随表现。
