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 status, there is little information about the doses at which these effects occur, the extent of the immune alterations and whether morphine's immunomodulatory effects can be antagonized in a dose-dependent manner 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 blood were collected. Immune status was assessed by a variety of in vitro assays. For splenic lymphocytes, morphine induced a dose-dependent suppression of lymphocyte function as measured by mitogen-induced proliferation, 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 contrast, morphine did not alter the capability of lymphocytes in the mesenteric lymph nodes to proliferate or produce cytokines. In a separate study, naltrexone (0, 0.1, 1.0 or 10.0 mg/kg) was administered before the injection of morphine (15 mg/kg). The results show that the immunomodulatory effects of morphine are antagonized by naltrexone. Collectively, the results of this investigation show that morphine's immunomodulatory effects are dose dependent, compartment specific and antagonized by naltrexone.