Changes in corticosteroid sensitivity of peripheral blood lymphocytes after strenuous exercise in humans
RH DeRijk, J Petrides, P Deuster, PW Gold and EM Sternberg
Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1284, USA.
Although plasma corticosteroid concentrations can be measured accurately,
the biological effect on the target tissue is uncertain. The availability
of an accurate measure of corticosteroid sensitivity would potentially
clarify the putative roles of endogenous glucocorticoids in illnesses such
as inflammatory disease and obesity and allow evaluation of an additional
regulatory level of glucocorticoid action. To measure corticosteroid
sensitivity, we developed an assay based on the inhibition by dexamethasone
(Dex) of lipopolysaccharide (LPS)-induced Interleukin-6 (IL-6) production
and release in whole unseparated blood in vitro. 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 dose dependently inhibited
LPS-induced IL-6 production. Involvement of the glucocorticoid receptor in
this response was supported by abrogation of Dex (10(-7) mol/L) inhibition
of IL-6 production by the glucocorticoid receptor antagonist RU 38486. To
determine whether corticosteroid 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- induced IL-6 production in vitro; after exercise, 3 x
10(-8) and 10(-7) mol/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 determining corticosteroid sensitivity, and that
corticosteroid sensitivity in human subjects is a dynamic, rather than a
static, phenomenon.
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