MORPHINE-INDUCED ALTERATIONS OF IMMUNE STATUS - DOSE DEPENDENCY, COMPARTMENT SPECIFICITY AND ANTAGONISM BY NALTREXONE

Although there is evidence to suggest that morphine can alter immune s tatus, there is little information about the doses at which these effe cts occur, the extent of the immune alterations and whether morphine's immunomodulatory effects can be antagonized in a dose-dependent manne r by an opioid antagonist. To address these issues, morphine (0, 5.0, 10.0, 15.0 or 25.0 mg/kg) was administered s.c. to Lewis rats. One hr later, the spleen, mesenteric lymph nodes and a sample of peripheral b lood were collected. Immune status was assessed by a variety of in vit ro assays. For splenic lymphocytes, morphine induced a dose-dependent suppression of lymphocyte function as measured by mitogen-induced prol iferation, natural killer cell cytotoxicity, interleukin-2 production and interferon production. For blood lymphocytes, the mitogen-induced proliferative response was suppressed in a dose-dependent manner. In c ontrast, morphine did not alter the capability of lymphocytes in the m esenteric lymph nodes to proliferate or produce cytokines. In a separa te study, naltrexone (0, 0.1, 1.0 or 10.0 mg/kg) was administered befo re the injection of morphine (15 mg/kg). The results show that the imm unomodulatory effects of morphine are antagonized by naltrexone. Colle ctively, the results of this investigation show that morphine's immuno modulatory effects are dose dependent, compartment specific and antago nized by naltrexone.