Evidence for beta adrenergic receptor involvement in the immunomodulatory effects of morphine.

The present study assessed the involvement of the beta adrenergic system in the immunomodulatory effects of morphine. Male Lewis rats were administered either the nonselective beta adrenergic antagonist nadolol, the beta 1-selective adrenergic antagonist atenolol or the beta 2-selective adrenergic antagonist erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobuta n-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 rat and multiple in vitro immune assays were performed. Pretreatment with all three beta adrenergic antagonists completely antagonized the suppressive effects of morphine on the proliferative responses of splenic leukocytes to concanavalin-A (Con-A), phytohemagglutinin (PHA), lipopolysaccharide (LPS) and the combination of ionomycin and phorbol myristate acetate (PMA). None of the antagonists blocked the suppressive effects of morphine on the proliferative responses of blood leukocytes to concanavalin-A or phytohemagglutinin, splenic natural killer (NK) cell activity, total splenic leukocyte counts and blood leukocyte counts per milliliter. These results demonstrate the involvement of beta adrenergic receptors in certain of morphine's immunosuppressive effects. Moreover, because both nadolol and atenolol are peripherally acting compounds, these data implicate peripheral beta adrenergic receptors specifically in morphine's immunomodulatory effects.