Weed Michael R, Carruth Lucy M, Adams Robert J, Ator Nancy A, Hienz Robert D
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, BBRC Suite 3000, 5510 Nathan Shock Drive, Baltimore, MD 21224, USA.
J Neuroimmune Pharmacol. 2006 Sep;1(3):250-9. doi: 10.1007/s11481-006-9029-z. Epub 2006 Jul 14.
The immune effects of chronic opiate exposure and/or opiate withdrawal are not well understood. The results of human studies with opiate abusers are variable and may not be able to control for important factors such as subjects' drug histories, health and nutritional status. Nonhuman primate models are necessary to control these important factors. A model of opiate dependence in macaques was developed to study the effects of opiate dependence and withdrawal on measures of immune function. Four pigtailed macaques drank a mixture of morphine (20 mg/kg/session) and orange-flavored drink every 6 h for several months. During stable morphine dependence, absolute numbers of neutrophils, monocytes and lymphocytes did not change relative to pre-morphine levels. However, there was a significant decrease in the absolute number and percentage of natural killer (NK) cells in morphine dependence. Either precipitated withdrawal or abstinence for 24 h resulted in behavioral withdrawal signs in all animals. Absolute lymphocyte counts decreased and absolute netrophil counts increased significantly in withdrawal, relative to levels during morphine dependence. Lymphocyte subset (CD4+, CD8+, CD20+) cells were also decreased in absolute numbers with little change in their percentage distributions. There was, however, a significant increase in the percentage of NK cells in withdrawal relative to levels during morphine dependence. This study demonstrates the usefulness of voluntary oral self-dosing procedures for maintaining morphine dependence in nonhuman primates and demonstrates that the morphine withdrawal syndrome includes large alterations in blood parameters of immune system function, including nearly 50% reduction in numbers of CD4+, CD8+ and CD20+ cells.
长期接触阿片类药物和/或阿片类药物戒断的免疫效应尚未得到充分了解。对阿片类药物滥用者进行的人体研究结果参差不齐，可能无法控制诸如受试者的用药史、健康状况和营养状况等重要因素。需要用非人类灵长类动物模型来控制这些重要因素。为了研究阿片类药物依赖和戒断对免疫功能指标的影响，建立了猕猴阿片类药物依赖模型。四只猪尾猕猴连续几个月每6小时饮用一次吗啡（20毫克/千克/次）与橙汁饮料的混合物。在稳定的吗啡依赖期，中性粒细胞、单核细胞和淋巴细胞的绝对数量相对于吗啡给药前水平没有变化。然而，吗啡依赖期自然杀伤（NK）细胞的绝对数量和百分比显著下降。突然戒断或戒断24小时会导致所有动物出现行为戒断症状。与吗啡依赖期相比，戒断期淋巴细胞绝对计数下降，中性粒细胞绝对计数显著增加。淋巴细胞亚群（CD4 +、CD8 +、CD20 +）细胞的绝对数量也减少，但其百分比分布变化不大。然而，与吗啡依赖期相比，戒断期NK细胞的百分比显著增加。这项研究证明了自愿口服自我给药程序在维持非人类灵长类动物吗啡依赖方面的有效性，并表明吗啡戒断综合征包括免疫系统功能血液参数的大幅改变，包括CD4 +、CD8 +和CD20 +细胞数量减少近50%。
