Bidirectional heterologous desensitization of opioid and chemokine receptors

Opioids are known to suppress a number of elements of the immune response, including antimicrobial resistance, antibody production, and delayed-type hypersensitivity. Phagocytic cells may be particularly susceptible to opioid administration, since reduced production of the cytokines IL-1, IL-6 and TNF-alpha, monocyte-mediated phagocytosis, and both neutrophil and monocyte chemotaxis have all been well established. Earlier studies have shown that both mu- and delta-opioid agonists induce a chemotactic response in monocytes and neutrophils. In addition, mu- and delta-opioid administration inhibited the chemotactic response of these cell populations to a number of chemokines through a process of heterologous desensitization. We report here that mu-, delta-, and kappa-opioid agonists also induce a chemotactic response in T lymphocytes. Using the human T-cell line Jurkat, we have confirmed previous observations that pre-incubation with met-enkephalin (MetEnk), an endogenous opioid agonist, prevents the subsequent chemotactic response to the chemokine RANTES. On the other hand, treatment with MetEnk does not alter the response to the chemokine SDF-1 alpha. Moreover, we found that pre-treatment with RANTES prevented a subsequent response of monocytes to the mu-opioid agonist DAMGO. These results suggest that activation of members of the opioid and chemokine receptor families leads to downregulation of each other's leukocyte migratory activities.