Strategies for blocking the systemic effects of cytokines in the sepsis syndrome.

Abstract

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.

• Authors: J W Christman, E P Holden, T S Blackwell
• Journal: Critical care medicine (Crit Care Med) Vol. 23 Issue 5 Pg. 955-63 (May 1995) ISSN: 0090-3493 [Print] United States
• PMID: 7736757 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Cytokines
• Receptors, Cytokine

Topics

• Animals
• Clinical Trials as Topic
• Cytokines (antagonists & inhibitors, physiology)
• Humans
• Receptors, Cytokine (antagonists & inhibitors, drug effects)
• Systemic Inflammatory Response Syndrome (etiology, physiopathology, therapy)
• Time Factors