STRATEGIES FOR BLOCKING THE SYSTEMIC EFFECTS OF CYTOKINES IN THE SEPSIS SYNDROME

Objectives: To review and evaluate animal and human data regarding str ategies to intervene in the pathogenesis of the sepsis syndrome by spe cifically blocking the action of single cytokines. Data Sources: The E nglish language medical literature was reviewed, including reports of human clinical trials, animal experiments, and in vitro studies elucid ating cellular and molecular interactions. Study Selection: Emphasis w as placed on controlled experimental studies that elucidated the effec tiveness of antibodies, soluble receptors, and receptor antagonists in intervening in the pathogenesis of the sepsis reaction. Data Extracti on: This review focuses on data that directly involve the induction an d regulation of protein mediators of sepsis, especially tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interleukin-8. D ata Synthesis: Information concerning the potential of cytokine blocke rs in modulating the sepsis reaction is presented in a logical, clinic ally oriented fashion. The purpose is to emphasize the potential role of these agents by focusing on the actual existing data. Conclusions: The pathophysiology of the sepsis reaction appears to involve the sequ ential release of cytokines. Interventions designed to specifically bl ock the biological effects of single cytokines appear to have a role i n the management of sepsis syndrome, but well-designed, prospective, r andomized, placebo-controlled clinical trials in well-defined clinical population are necessary to define this role. These trials require th e cooperation of clinical and basic scientists.