Suppressive effects of morphine pellet implants on in vivo parameters of immune function

Chronic morphine treatment elicits a variety of immunosuppressive effects in mice. Most of the work describing this immuno-suppressive activity of the opioid is based on in vitro assessments of the performance of certain components of the immune system in morphine-treated animals. Relatively little has been done by way of tracking the effects of chronic morphine treatment on immunologic parameters in the intact animal. Therefore, this study used several classic in vivo determinations of immune function in mice treated chronically with morphine. Morphine pellet (75 mg) implantation led to a significant inhibition (91%) of paw swelling in a picryl chloride-induced delayed type hypersensitivity response. Uptake of iododeoxyuridine in an in vivo lymphocyte proliferation assay and splenomegaly in a graft vs. host reaction were also significantly suppressed by morphine pellet implantation (34 and 52%, respectively). Coimplantation of a naltrexone pellet (10 mg) completely reversed the suppressive responses to morphine in each assay. Naltrexone alone had no significant effect in any of the assays. The suppressive effects of morphine were less pronounced in adrenalectomized mice in the graft vs. host assay (51% vs. 9% reduction in morphine-pelleted shams relative to morphine-pelleted adrenalectomized mice). These findings indicate the pathophysiologic significance of the previously reported suppression of in vitro correlates of immune function in morphine-pelleted mice. The results further demonstrate that the immunosuppressive effects observed after morphine pellet implantation are naltrexone reversible and suggest that activation of the adrenal is one potential mechanism for this effect.