MODULATION OF SIMIAN AIDS BY OPIOIDS

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Significance Chemokines, characterized as pro-inflammatory chemicals made by the immunesystem, consist of a family of low molecular weight proteins with potent in vitro chemotactic activity causing leukocyte accumulation in vivo. In general, the a chemokines (C-X-C, C denotes cysteines) such as interleukin-8 (IL-8) induce chemotaxis in polymorphonuclear cells (PMN) and have no effect on monocytes, while the b chemokines (C-C) such as RANTES, MIP-1a and MIP-1b predominantly chemoattract monocytes, macrophages and T cells. Objectives This study determined the effect of opioid treatment on the chemotactic functions of PMN and monocytes isolated from monkey leukocytes using a 48-well chemotaxis chamber. Monkey PMN or monocytes were treated with morphine or morphine antagonist for 1 hr at 370C, and the number of cells migrating toward 200 ng/ml IL-8 (for PMN) or 100 ng/ml RANTES (for monocytes) were scored. Results Inhibition of chemotaxis was seen with all animal samples after treatment with morphine at 10-4 M. Decreasing concentrations of morphine showed increasing chemotaxis with 10-14 M concentration bringing the number of cells equal to that of positive control (no morphine treatment.) Naloxone, an antagonist to morphine, was added 30 minutes prior to the addition of morphine sulfate to the cells. When the morphine concentration used was 10-6 M, naloxone at 10-4 M was able to reverse the morphine inhibitory effect on PMN chemotaxis by 85% while naloxone at equal molar of morphine (10-6 M) reversed the inhibition by 69%. Similar morphine and morphine/naloxone effects on monocyte chemotaxis toward RANTES were observed. These studies suggest that opiate abuse caused defects in host defense and may have implications for the enhanced immunosuppression seen with AIDS patients of opiate users. Future Directions Future directions will include the evaluation of the effects of other opioids and opioid antagonists in this study. KEYWORDS rhesus monkeys, peripheral blood mononuclear cells, monocytes, PMN, chemokines, chemotaxis, morphine and other opioids