Biology of proinflammatory cytokines and their antagonists.

OBJECTIVES

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.

DATA SOURCES

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.

STUDY SELECTION

Controlled animal studies that elucidate the relationship between TNF-alpha and IL-1, and endotoxin-induced shock were selected for review.

DATA EXTRACTION

This review focused on those data that described the roles of IL-1 and TNF-alpha in the induction of the inflammatory cascade.

DATA SYNTHESIS

Information concerning the many aspects of attenuating the systemic inflammatory response was integrated into a description of emerging therapies for septic shock.

CONCLUSIONS

Induction of inflammation during sepsis is a complex biological cascade that may be effectively attenuated by novel anticytokine biotherapies.