Opioid-mediated suppression of interferon-gamma production by cultured peripheral blood mononuclear cells.
Opioid-mediated suppression of interferon-gamma production by cultured peripheral blood mononuclear cells.
复制标题
DOI：
10.1172/jci113140
复制
发表时间：
1987-09
期刊：
影响因子：
--
通讯作者：
Phillip K. Peterson;B. Sharp;G. Gekker;C. Brummitt;W. Keane
中科院分区：
文献类型：
--
作者：
Phillip K. Peterson;B. Sharp;G. Gekker;C. Brummitt;W. Keane
越来越多的证据表明，阿片成瘾和压力与细胞介导的免疫功能受损有关。我们验证了吗啡和内源性阿片样物质β -内啡肽（β -end）（一种在应激状态下浓度增加的垂体肽）可以抑制培养的人外周血单核细胞（PBMNC）产生关键的巨噬细胞激活淋巴因子干扰素γ (ifn - γ)的假设。使用放射免疫测定法测量ifn - γ，我们发现PBMNC暴露于两种阿片类药物的生物学相关浓度下，可显著抑制受豆豆蛋白a和水痘带状疱疹病毒刺激的细胞产生ifn - γ。抑制机制的研究表明：(a)一种经典的阿片受体参与其中（抑制被纳洛酮拮抗，并且特异性针对β - end的NH2端），(b)单核细胞是阿片的主要靶细胞（单核细胞耗尽的淋巴细胞制剂几乎没有抑制），(c)活性氧中间体（ROI）和前列腺素E2是重要的介质（ROI和吲哚美辛清剂消除了抑制）。基于这些发现，我们认为阿片类药物引发的抑制性单核细胞代谢物的释放可能在与麻醉成瘾和应激相关的免疫缺陷中发挥作用。
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.