CHANGES IN CORTICOSTEROID SENSITIVITY OF PERIPHERAL-BLOOD LYMPHOCYTESAFTER STRENUOUS EXERCISE IN HUMANS

Although plasma corticosteroid concentrations can be measured accurate ly, the biological effect on the target tissue is uncertain. The avail ability of an accurate measure of corticosteroid sensitivity would pot entially clarify the putative roles of endogenous glucocorticoids in i llnesses such as inflammatory disease and obesity and allow evaluation of an additional regulatory level of glucocorticoid action. To measur e corticosteroid sensitivity, we developed an assay based on the inhib ition by dexamethasone (Dex) of lipopolysaccharide (LPS)-induced Inter leukin-6 (IL-6) production and release in whole unseparated blood in v itro. LPS induced a dose-dependent increase in IL-6 concentrations up to 34 +/- 6.6 ng/mL, reaching plateau levels after 8 h, whereas Dex do se dependently inhibited LPS-induced IL-6 production. Involvement of t he glucocorticoid receptor in this response was supported by abrogatio n of Dex (10(-7) mol/L) inhibition of IL-6 production by the glucocort icoid receptor antagonist RU 38486. To determine whether corticosteroi d sensitivity is a dynamic phenomenon, we subjected healthy males to a graded quantifiable exercise associated with increases in plasma ACTH and cortisol. Before exercise, 3 x 10(-8) mol/L Dex inhibited LPS-ind uced IL-6 production in vitro; after exercise, 3 x 10(-8) and 10(-7) m ol/L Dex were unable to inhibit IL-6 production. We conclude that Dex suppression of LPS-induced IL-6 production is an effective means of de termining corticosteroid sensitivity and that corticosteroid sensitivi ty in human subjects is a dynamic, rather than a static, phenomenon.