THE OPIOID-CYTOKINE CONNECTION

Opioids (exogenous opiates and endogenous opioid peptides) have a dive rsity of effects on the immune system. Although numerous studies have shown that opioid-induced immunosuppression can be mediated indirectly via the central nervous system (CNS) or through direct interactions w ith immunocytes, the precise cellular mechanisms underlying the immuno modulatory effects of opioids are largely unknown. In recent years, in vestigations from several laboratories have indicated that opioids can operate as cytokines, the principal communication signals of the immu ne system. All of the major properties of cytokines are shared by opio ids, i.e., production by immune cells with paracrine, autocrine, and e ndocrine sites of action, functional redundancy, pleiotropy and effect s that are both dose- and time-dependent. Studies of the effects of op ioids on peripheral blood mononuclear cells (PBMC) or brain cells cocu ltured with HIV-infected cells suggest that some of the immunoregulato ry actions of opioids are mediated by ultrahigh affinity receptors on PBMC and glial cells. Because the CNS is populated predominantly by as troglia and microglia which have properties of immune cells, it is pos sible that certain of the CNS effects of opioids involve cytokine-like interactions with glial cells. Although there is mounting evidence su pporting the concept that opioids are members of the cytokine family, the relative contribution of the opioids to immunoregulation remains u nclear. The importance of opiate addiction in the AIDS epidemic means that gaining a better understanding of the mechanisms of opioid-induce d immunomodulation is of more than academic interest. (C) 1998 Elsevie r Science B.V.