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Tumor necrosis factor-alpha (TNF) has been implicated as an important, proximal mediator of many of the pathophysiologic effects observed during septic shock. In vitro studies have demonstrated that the glucocorticoid dexamethasone (Dex) will suppress the production of TNF; yet, clinical studies have shown that glucocorticoids are not protective in septic shock. In this paper we described the in vivo effects of lipopolysaccharide (LPS) on the kinetics of local and systemic TNF production, the time dependent expression of TNF mRNA, and the suppression of both TNF mRNA and bioactive protein using a defined treatment protocol of Dex. Peritoneal macrophages were elicited by CBA/J mice in the injection of complete Freunds adjuvant and the mice challenged with an intraperitoneal injection of LPS 2 weeks later. Kinetic studies showed that the peak of TNF production occurred 1 hour post LPS injection and reached a maximum of 775 units/ml within the ascites and 26 units/ml within the plasma. Northern blot analysis of mRNA extracted from peritoneal cells showed a peak of mRNA 30 minutes post LPS challenge. Dose-response studies disclosed that 10 micrograms of LPS/mouse produced maximal TNF within the ascites fluid, and half-maximal stimulation occurred at 70 ng LPS/mouse. Mice treated with Dex in vivo before LPS challenge showed a dramatic reduction in TNF production within both the ascites and plasma, and Northern blot analysis showed a corresponding reduction in the TNF specific mRNA. Further studies revealed that mice treated with 4 mg/kg of Dex intraperitoneally 4 hours before, or at the time of LPS challenge, had …