Fisher C J, Opal S M, Lowry S F, Sadoff J C, LaBrecque J F, Donovan H C, Lookabaugh J L, Lemke J, Pribble J P, Stromatt S C
Department of Pulmonary and Critical Care Medicine, Cleveland Clinic Foundation, OH 44195, USA.
Circ Shock. 1994 Sep;44(1):1-8.
Clinical trials of anticytokines in sepsis have not been as straightforward as had been anticipated from results in animal models of sepsis and the role of cytokines in sepsis is now in question. Retrospective analysis of the results of a phase III trial of interleukin-1 (IL-1) receptor antagonist suggests that sepsis-induced adult respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), renal dysfunction, and shock are valuable markers of patients in whom IL-1 is a pathogenic mediator and in whom IL-1ra can reduce mortality. A re-examination of the effects of IL-1ra in animal models of sepsis supports the validity of this analysis. A new phase III clinical trial will confirm or disprove the hypothesis that IL-1 is a mediator of pathology, and IL-1ra is a valuable therapy for sepsis complicated by ARDS, DIC, renal dysfunction, or shock.
抗细胞因子在脓毒症中的临床试验并不像脓毒症动物模型的结果所预期的那样简单直接，细胞因子在脓毒症中的作用现在受到质疑。对白介素-1（IL-1）受体拮抗剂III期试验结果的回顾性分析表明，脓毒症诱导的成人呼吸窘迫综合征（ARDS）、弥散性血管内凝血（DIC）、肾功能不全和休克是IL-1作为致病介质且IL-1受体拮抗剂（IL-1ra）可降低死亡率的患者的重要标志物。对IL-1ra在脓毒症动物模型中作用的重新审视支持了这一分析的有效性。一项新的III期临床试验将证实或反驳IL-1是病理介质且IL-1ra是治疗并发ARDS、DIC、肾功能不全或休克的脓毒症的有效疗法这一假设。
