Opioid-mediated suppression of interferon-gamma production by cultured peripheral blood mononuclear cells. 1987

P K Peterson, and B Sharp, and G Gekker, and C Brummitt, and W F Keane

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 beta-endorphin (beta-END), a pituitary peptide released in increased concentrations during stress, can suppress the production of the key macrophage-activating lymphokine interferon-gamma (IFN-gamma) by cultured human peripheral blood mononuclear cells (PBMNC). Using a radioimmunoassay to measure IFN-gamma, we found that exposure of PBMNC to biologically relevant concentrations of both opioids significantly inhibited IFN-gamma generation by cells stimulated with concanavalin 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 beta-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.

UI MeSH Term Description Entries
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D009020 Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D011957 Receptors, Opioid Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known. Endorphin Receptors,Enkephalin Receptors,Narcotic Receptors,Opioid Receptors,Receptors, Endorphin,Receptors, Enkephalin,Receptors, Narcotic,Receptors, Opiate,Endorphin Receptor,Enkephalin Receptor,Normorphine Receptors,Opiate Receptor,Opiate Receptors,Opioid Receptor,Receptors, Normorphine,Receptors, beta-Endorphin,beta-Endorphin Receptor,Receptor, Endorphin,Receptor, Enkephalin,Receptor, Opiate,Receptor, Opioid,Receptor, beta-Endorphin,Receptors, beta Endorphin,beta Endorphin Receptor,beta-Endorphin Receptors
D001773 Blood Cells The cells found in the body fluid circulating throughout the CARDIOVASCULAR SYSTEM. Blood Corpuscles,Blood Cell,Blood Corpuscle,Cell, Blood,Cells, Blood,Corpuscle, Blood,Corpuscles, Blood
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003208 Concanavalin A A MANNOSE/GLUCOSE binding lectin isolated from the jack bean (Canavalia ensiformis). It is a potent mitogen used to stimulate cell proliferation in lymphocytes, primarily T-lymphocyte, cultures.
D004723 Endorphins One of the three major groups of endogenous opioid peptides. They are large peptides derived from the PRO-OPIOMELANOCORTIN precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; OPIOID PEPTIDES is used for the broader group. Endorphin

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