GLUCOCORTICOIDS ALTER FEVER AND IL-6 RESPONSES TO PSYCHOLOGICAL STRESS AND TO LIPOPOLYSACCHARIDE

The purpose of this study was to determine whether glucocorticoids exe rt inhibitory feedback on lipopolysaccharide (LPS)-induced fever, stre ss-induced fever (exposure to an open field), and plasma concentration s of interleukin-6 (IL-6)-like and tumor necrosis factor-alpha (TNF)-l ike activity in biotelemetered rats. Injections of LPS (50 mug/kg) or exposure to an open field (30 min) led to significantly higher fevers in adrenalectomized (ADX) rats than in sham-ADX rats. To test the hypo thesis that higher fevers were specifically the result of an absence o f glucocorticoids, the glucocorticoid antagonist RU 38486 (20 mg/kg) w as administered orally to rats with intact adrenal glands. The RU 3848 6-treated rats had higher plasma concentrations of IL-6-like activity and developed significantly higher fevers than did vehicle-treated rat s. Rats injected intracerebroventricularly with 10 ng RU 38486 also de veloped higher fevers. Other ADX animals were implanted subcutaneously with replacement corticosterone pellets before exposure to an open fi eld or injection with LPS. In response to an open field or injection w ith LPS, ADX animals implanted with replacement pellets that mimic pla sma concentrations of corticosterone observed in stressed animals (100 -mg pellets) developed fevers that were significantly lower than those observed in ADX rats given placebo pellets, but that were not differe nt from fevers in sham-ADX rats given placebo pellets. ADX animals imp lanted with replacement pellets that mimic plasma concentrations of co rticosterone observed in unstressed animals (25-mg pellets) developed fevers that were significantly higher than those observed in sham-ADX rats given placebo pellets, but that were not different from fevers in ADX rats given placebo pellets. We conclude that elevated glucocortic oids exert an inhibitory feedback on LPS-induced fever, fever induced by psychological stress, and plasma concentrations of IL-6-like activi ty at the height of both fevers.