IMMUNOREGULATORY EFFECTS OF MORPHINE ON HUMAN-LYMPHOCYTES

It is now well established that parenteral drug abuse is a significant risk factor for contracting human immunodeficiency virus type 1 (HIV- 1) infection and subsequently developing AIDS. Earlier studies have sh own that morphine can modulate various immune responses and therefore support the premise that morphine is a cofactor in susceptibility to a nd progression of HIV infection. Dysregulation of interferon (IFN) pro duction, nonspecific apoptosis of T cells, and the immune response to soluble HIV gene products have been associated with potential mechanis ms of pathogenesis in HN disease. The present study was undertaken to examine the immunomodulatory role of morphine on HN protein-induced ly mphocyte proliferative responses, Sendai and Newcastle disease virus-i nduced alpha IFN (IFN-alpha) and IFN-beta production by lymphocytes an d fibroblast cells, respectively, and induction of apoptosis of normal lymphocytes in vitro. Our results demonstrate that HN protein-induced human lymphocyte proliferative responses were significantly inhibited by morphine in a dose-dependent manner. Furthermore, morphine signifi cantly inhibited both IFN-alpha and IFN-beta production by normal lymp hocytes and fibroblasts but induced apoptosis of normal lymphocytes. I nhibition of IFN-alpha production by morphine could be reversed by the opiate receptor antagonist naloxone. This suggests that the immunomod ulatory effects of morphine are mediated through the opioid receptor. These studies support a role of morphine as a cofactor in the pathogen esis of HIV infection and describe some of the possible pathologic mec hanisms which underlie the immunoregulatory effects of morphine.