Mediators of septic shock: new approaches for interrupting the endogenous inflammatory cascade.
OBJECTIVE
To review the molecular pathogenesis of septic shock, with particular emphasis on the induction of cytokines by endotoxin. By understanding the mechanisms that result in the systemic inflammatory response, novel clinical interventions may be more effectively studied.


METHODS
The English medical literature was reviewed, including human clinical trials, animal experiments, and in vitro studies elucidating cellular and molecular interactions. Expert testimony from the Roundtable Conference on Sepsis (Brussels, March 1992) was also used to synthesize emerging concepts and to ensure inclusion of ongoing investigations.


METHODS
Emphasis on controlled experimental studies which elucidated the molecular and cellular interactions during sepsis.


METHODS
This study focused only on data that directly involved the induction and regulation of protein mediators of sepsis, especially tumor necrosis factor (TNF) and interleukin-1. Data concerning the role of TNF during health were extracted from the author's peer-reviewed data.


RESULTS
Information concerning the many facets of the systemic inflammatory response was integrated into a chronological, clinically oriented model of cytokine induction during endotoxemia.


CONCLUSIONS
The induction of inflammation during sepsis is a complex, but increasingly understood, biological cascade that is dependent on inter- and intracellular signaling. Novel biotherapies may improve patient outcome in sepsis by interrupting any or all points of signal transduction.
Giroir
B P
BP
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D016905:Gram-Negative Bacterial Infections / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology; D008070:Lipopolysaccharides / Q000032:analysis / Q000494:pharmacology; D008967:Molecular Biology; D012772:Shock, Septic / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology
D000900:Anti-Bacterial Agents; D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha