Immunosuppressive effects of chronic morphine treatment in mice

In this report we describe the immunomodulatory effects of subcutaneous morphine pellets in mice, a model commonly used in the study of opiate tolerance and dependence. Mice given a single 75 mg morphine pellet displayed marked atrophy and reduced cellularity of the spleen and thymus, and an attenuated lymphocyte proliferative response to T- and B-cell mitogens (concanavalin A and bacterial lipopolysaccharide, respectively). These immunosuppressive effects were observed 72 hr following implantation of the pellet, a time point by which the mice also had developed tolerance to the antinociceptive effect of the pellet. Splenic and thymic atrophy with reduced mitogen-induced lymphocyte proliferative responses and opiate tolerance were also apparent in mice subjected to a multiple pellet implantation schedule. However, implantation of a pellet containing 37.5 mg morphine did not suppress mitogen-stimulated lymphocyte proliferation, which was slightly elevated in this group. These findings concur with other observations suggesting immunosuppression with morphine tolerance. Furthermore, we suggest that chronic morphine treatment acts as a pharmacologic stressor that mimics behavioral stress.