Biology of proinflammatory cytokines and their antagonists.

Abstract

To review the role of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) in the proinflammatory cascade, with particular emphasis on the association between increased concentrations of these cytokines and the sepsis-associated shock syndrome. Data that support the role of these cytokines as proinflammatory mediators provide a rationale for specific anticytokine therapies. Information presented at the 22nd Educational and Scientific Symposium of the Society of Critical Care Medicine on June 9-13, 1993 in New York City was reviewed, along with supportive documentation from the English language literature. Controlled animal studies that elucidate the relationship between TNF-alpha and IL-1, and endotoxin-induced shock were selected for review. This review focused on those data that described the roles of IL-1 and TNF-alpha in the induction of the inflammatory cascade. Information concerning the many aspects of attenuating the systemic inflammatory response was integrated into a description of emerging therapies for septic shock. Induction of inflammation during sepsis is a complex biological cascade that may be effectively attenuated by novel anticytokine biotherapies.