Peterson P K, Sharp B M, Gekker G, Portoghese P S, Sannerud K, Balfour H H
Department of Medicine, Hennepin County Medical Center, Minneapolis, MN 55415.
AIDS. 1990 Sep;4(9):869-73. doi: 10.1097/00002030-199009000-00006.
Because morphine has been shown to alter the function of human T lymphocytes and monocytes, we postulated that morphine would promote the growth of HIV-1 in these cells. To test this hypothesis, a coculture assay was used consisting of phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells (PBMC) from normal donors and PBMC which had been infected with a viral isolate from an asymptomatic patient, HIV-1AT. The growth of HIV-1AT, as reflected by the concentration of p24 antigen in coculture supernatants, was markedly increased in cocultures that contained morphine. A bell-shaped dose-response curve was observed with three- to fourfold increased growth at a morphine concentration of 10(-12) M. Augmentation of HIV-1AT growth by morphine required an interaction with the PHA-activated donor PBMC. Furthermore, potentiation of HIV-1AT growth by morphine was stereospecific and was antagonized by naloxone and beta-funaltrexamine indicating involvement of an opiate receptor mechanism. These findings provide an additional explanation of how opiates could act as a cofactor in the pathogenesis of HIV-1 in intravenous drug users.
由于吗啡已被证明会改变人类T淋巴细胞和单核细胞的功能,我们推测吗啡会促进HIV-1在这些细胞中的生长。为了验证这一假设,我们采用了一种共培养试验,该试验由来自正常供体的经植物血凝素(PHA)激活的外周血单核细胞(PBMC)和感染了一名无症状患者的病毒分离株HIV-1AT的PBMC组成。如共培养上清液中p24抗原浓度所反映的,HIV-1AT的生长在含有吗啡的共培养物中显著增加。在吗啡浓度为10(-12)M时观察到呈钟形的剂量反应曲线,生长增加了三到四倍。吗啡增强HIV-1AT生长需要与PHA激活的供体PBMC相互作用。此外,吗啡对HIV-1AT生长的增强具有立体特异性,且被纳洛酮和β-氟纳曲胺拮抗,表明涉及阿片受体机制。这些发现为阿片类药物如何在静脉吸毒者中作为HIV-1发病机制的辅助因素提供了另一种解释。