INFLUENCE OF HYPERCORTISOLEMIA ON SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR-II AND INTERLEUKIN-1 RECEPTOR ANTAGONIST RESPONSES TO ENDOTOXIN INHUMAN-BEINGS

Background. We have previously reported that the antecedent administra tion of glucocorticoids altered both the hormonal and proinflammatory cytokine responses to lipopolysaccharide (LPS) when administered to hu man volunteers. In that study, subjects with vastly exaggerated levels of tumor necrosis factor (TNF) and interleukin (IL)-6 12 and 144 hour s after cortisol infusion exhibited hemodynamic and hormonal responses no different from those of untreated subjects after endotoxin. The cu rrent study examined levels of the antiinflammatory cytokines interleu kin-1 receptor antagonist (IL-1ra) and soluble receptors to tumor necr osis factor (sTNF-R) in the same setting of the previous report. Metho ds. Hydrocortisone succinate was infused into healthy volunteers. LPS was then injected immediately or was delayed by 6, 12, or 144 hours (C , C-6, C-12, and C-144, respectively). Subjects receiving LPS alone se rved as controls. Plasma was analyzed to determine levels of TNF, sTNF -R and IL-1ra by enzyme-linked immunosorbent assay before administrati on of LPS and at 30-minute intervals after administration of LPS for 6 hours. Results. Levels of sTNF-R increased after PS administration in all groups (p < 0.05 versus baseline) with a significantly higher lev el recorded in the subjects having received hydrocortisone 144 hours b efore (C-144, p < 0.05 versus all other groups). TNF levels remained u ndetectable in association with immediate infusion of LPS (C) and the relatively short delay group (C6). This cytokine peaked 90 minutes aft er LPS in all other groups, with a significantly higher peak in the C- 144 subjects when compared with controls. IL-1ra levels rose in all gr oups but to a lesser extent in the C group (p < 0.05). Conclusions. Th ese data confirm that glucorticoids influence the production of both s TNF-R and IL-1ra. The potential for an exaggerated response of sTNF-R exists for an extended period of time after exposure to glucocorticoid s.