mu-opioid induction of monocyte chemoattractant protein-1, RANTES, and IFN-gamma-inducible protein-10 expression in human peripheral blood mononuclear cells

Strong evidence for the direct modulation of the immune system by opioids i s well documented. mu -Opioids have been shown to alter the release of cyto kines important for both host defense and the inflammatory response. Proinf lammatory chemokines monocyte chemoattractant protein-1 (MCP-1), RANTES, an d IFN-gamma -inducible protein-10 (IP-10) play crucial roles in cell-mediat ed immune responses, proinflammatory reactions, and viral infections. In th is report, we show that [D-Ala(2),N-Me-Phe(4),Gly-ol(5)]enkephalin (DAMGO), a mu -opioid-selective agonist, augments the expression in human PBMCs of MCP-I, RANTES, and IP-10 at both the mRNA and protein levels, Because of th e proposed relationship between opioid abuse and HIV-1 infection, we also e xamined the impact of DAMGO on chemokine expression in HIV-infected cells, Our results show that DAMGO administration induces a significant increase i n RANTES and IP-10 expression, while MCP-I protein levels remain unaffected in PBMCs infected with the HIV-1 strain. In contrast, we show a dichotomou s effect of DAMGO treatment on IP-10 protein levels expressed by T-and M-tr opic HIV-infected PBMCs, The differential modulation of chemokine expressio n in T- and M-tropic HIV-1-infected PBMCs by opioids supports a detrimental role for opioids during HIV-1 infection. Modulation of. chemokine expressi on may enhance trafficking of potential noninfected target cells to the sit e of active infection, thus directly contributing to HIV-1 replication and disease progression to AIDS.