Mounting evidence suggests that opiate addiction and stress are associated with impaired cell-mediated immunity. We tested the hypothesis that morphine and the endogenous opioid fl-endorphin (f-END), a pituitary peptide released in increased concentrations during stress, can suppress the production of the key macrophage-activating lymphokine interferon-v (IFN-'y) by cultured human peripheral blood mononuclear cells (PBMNC). Using a radioimmunoassay to measure IFN-'y, we found that exposure of PBMNC to biologically relevant concentrations of both opioids significantly inhibited IFN-'y generation by cells stimulated with coucanavalin A and varicella zoster virus. Studies of the mechanism of suppression revealed (a) a classical opioid receptor is involved (suppression was antagonized by naloxone and was specific for the NH2 terminus of f-END), (b) monocytes are the primary target cell for opioids (monocyte-depleted lymphocyte preparations showed little suppression), and (c) reactive oxygen intermediates (ROI) and prostaglandin E2 are important mediators (scavengers of ROI and indomethacin eliminated the suppression). Based on these findings we suggest that opioid-triggered release of inhibitory monocyte metabolites may play a role in the immunodeficiency associated with narcotic addiction and stress.

When HIV-infected patients are exposed to cryptosporidium, those with CD4 counts < or = 50 per cubic millimeter are at increased risk for biliary symptoms and for death within one year after the infection.

Recent studies have shown that in vitro exposure of peripheral blood mononuclear cells (PBMC) to morphine results in suppressed respiratory-burst activity of monocytes and impaired interferon-gamma (IFN-gamma) production by lymphocytes. To investigate the potential in vivo effect of an opiate on these cell functions, PBMC were obtained from patients maintained on methadone. These freshly isolated mononuclear cells had a significantly impaired capacity to generate superoxide anion (O2-) in response to phorbol myristate acetate (PMA), while production of IFN-gamma by concanavalin A-stimulated cells was intact. After cell culture for 48 h, the defective O2- generating capacity was sustained. Also, culturing PBMC from healthy controls in the presence of methadone or morphine at concentrations as low as 10(-12) M caused significant suppression of PMA-stimulated O2- release. Because reactive oxygen intermediates produced by PBMC may participate in host defense against opportunistic pathogens in AIDS, these results underscore the need for investigations of the biological consequences of opiate-mediated immunosuppression.

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