ACUTE IMMUNOSUPPRESSIVE EFFECTS OF MORPHINE - LACK OF INVOLVEMENT OF PITUITARY AND ADRENAL FACTORS

We have previously reported that morphine inhibits Concanavalin A-stim ulated blood lymphocyte proliferation in a dose-dependent manner. Maxi mal (80%) inhibition by morphine occurred with a dose of 10 mg/kg 2 ho urs after drug administration. Concurrent with this suppressive effect was a 2- to 4-fold increase in plasma corticosterone concentrations. In the present study, we examined the potential contribution of the hy pothalamic-pituitary-adrenal axis to the suppressive effects of acute morphine exposure. To assess the role of glucocorticoids, rats were pr etreated with the steroid receptor antagonist RU486 (20 mg/kg) 30 min before morphine (10 mg/kg) administration. A significant inhibition of lymphocyte activity occurred with morphine in the absence or presence of RU486 pretreatment. Consistent with a mechanism independent of glu cocorticoids, adrenalectomy also failed to attenuate the inhibitory ac tions of morphine. To examine the potential role of pituitary hormones in the suppressive effect, similar experiments were carried out in hy pophysectomized animals. In sham-operated or hypophysectomized animals , morphine was found to be equally effective in suppressing lymphocyte proliferation. These results suggest that factors elaborated from int act pituitary or adrenal glands are not required for the acute inhibit ory effects of morphine on peripheral blood lymphocyte activity.