OBJECTIVES: To review and evaluate animal and human data regarding strategies to intervene in the pathogenesis of the sepsis syndrome by specifically blocking the action of single cytokines. DATA SOURCES: The English language medical literature was reviewed, including reports of human clinical trials, animal experiments, and in vitro studies elucidating cellular and molecular interactions. STUDY SELECTION: Emphasis was placed on controlled experimental studies that elucidated the effectiveness of antibodies, soluble receptors, and receptor antagonists in intervening in the pathogenesis of the sepsis reaction. DATA EXTRACTION: This review focuses on data that directly involve the induction and regulation of protein mediators of sepsis, especially tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interleukin-8. DATA SYNTHESIS: Information concerning the potential of cytokine blockers in modulating the sepsis reaction is presented in a logical, clinically 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 sequential release of cytokines. Interventions designed to specifically block the biological effects of single cytokines appear to have a role in the management of sepsis syndrome, but well-designed, prospective, randomized, placebo-controlled clinical trials in well-defined clinical populations are necessary to define this role. These trials require the cooperation of clinical and basic scientists.
OBJECTIVES: To review and evaluate animal and human data regarding strategies to intervene in the pathogenesis of the sepsis syndrome by specifically blocking the action of single cytokines. DATA SOURCES: The English language medical literature was reviewed, including reports of human clinical trials, animal experiments, and in vitro studies elucidating cellular and molecular interactions. STUDY SELECTION: Emphasis was placed on controlled experimental studies that elucidated the effectiveness of antibodies, soluble receptors, and receptor antagonists in intervening in the pathogenesis of the sepsis reaction. DATA EXTRACTION: This review focuses on data that directly involve the induction and regulation of protein mediators of sepsis, especially tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interleukin-8. DATA SYNTHESIS: Information concerning the potential of cytokine blockers in modulating the sepsis reaction is presented in a logical, clinically 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 sequential release of cytokines. Interventions designed to specifically block the biological effects of single cytokines appear to have a role in the management of sepsis syndrome, but well-designed, prospective, randomized, placebo-controlled clinical trials in well-defined clinical populations are necessary to define this role. These trials require the cooperation of clinical and basic scientists.