CYTOKINE APPEARANCE IN HUMAN ENDOTOXEMIA AND PRIMATE BACTEREMIA

Abstract

The results of recent work have demonstrated that endotoxin elicits the production of several immunopeptide cytokines that likely mediate the development of septic shock. Bolus injection of endotoxin (20 units per kilogram of body weight) to four volunteers resulted in peak serum cachetin/tumor necrosis factor (TNF) levels of 358 .+-. 166 picograms per milliliter within 90 minutes after challenge (p < 0.05 versus base line) and peak serum interleukin-1 levels of 21.4 .+-. 0.89 unit per milliliter within two hours after challenge. By contrast, the infusion of a lethal dose of live Escherchia coli to four baboons revealed peak serum cachetin/TNF levels of 20,500 .+-. 9,890 picograms per milliliter within 90 minutes after bacteria were given (p < 0.05 versus base line) and peak interleukin-1 levels of 14.2 .+-. 10.1 units per milliliter three hours after bacterial challenge. No detectable monokine levels were observed in either model six hours after challenge. Interferon-gamma levels reached a peak of 2.67 .+-. 1.66 nanograms per milliliter in baboon sera at eight hours after bacterial infusion and was no longer detectable by 12 hours. Interferon-gamma was not detected in the sera of humans. These results suggest that the transient release of cachectin/TNF, followed by interleukin-1 and interferon-gamma, may participate in the cascade of events noted in overwhelming bacterial invasion.