EVIDENCE FOR BETA-ADRENERGIC-RECEPTOR INVOLVEMENT IN THE IMMUNOMODULATORY EFFECTS OF MORPHINE

The present study assessed the involvement of the beta adrenergic syst em in the immunomodulatory effects of morphine. Male Lewis rats were a dministered either the nonselective beta adrenergic antagonist nadolol , the beta1-selective adrenergic antagonist atenolol or the beta2-sele ctive adrenergic antagonist (7-methylindan-4-yloxy)-3-isopropylaminobu tan-2-ol (ICI-118,551) in doses of 0, 0.125, 0.5, 2.0 or 8.0 mg/kg s.c . before the administration of 15 mg/kg morphine or saline s.c. After sacrifice, the spleen was removed and blood was collected from each ra t and multiple in vitro immune assays were performed. Pretreatment wit h all three beta adrenergic antagonists completely antagonized the sup pressive effects of morphine on the proliferative responses of splenic leukocytes to concanavalin-A (Con-A), phytohemagglutinin (PHA), lipop olysaccharide (LPS) and the combination of ionomycin and phorbol myris tate acetate (PMA). None of the antagonists blocked the suppressive ef fects of morphine on the proliferative responses of blood leukocytes t o concanavalin-A or phytohemagglutinin, splenic natural killer (NK) ce ll activity, total splenic leukocyte counts and blood leukocyte counts per milliliter. These results demonstrate the involvement of beta adr energic receptors in certain of morphine's immunosuppressive effects. Moreover, because both nadolol and atenolol are peripherally acting co mpounds, these data implicate peripheral beta adrenergic receptors spe cifically in morphine's immunomodulatory effects.