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


METHODS
The English language medical literature was reviewed, including reports of human clinical trials, animal experiments, and in vitro studies elucidating cellular and molecular interactions.


METHODS
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.


METHODS
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.


RESULTS
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.
Christman
J W
JW
Department of Veterans Affairs, Nashville, TN, USA.
Holden
E P
EP
Blackwell
T S
TS
D000818:Animals; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D018121:Receptors, Cytokine / Q000037:antagonists & inhibitors / Q000187:drug effects; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors
D016207:Cytokines; D018121:Receptors, Cytokine