LeVier D G, McCay J A, Stern M L, Harris L S, Page D, Brown R D, Musgrove D L, Butterworth L F, White K L, Munson A E
Department of Pharmacology and Toxicology, School of Dentistry, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.
Fundam Appl Toxicol. 1994 May;22(4):525-42. doi: 10.1006/faat.1994.1060.
This study was undertaken to investigate a number of immune parameters which may be compromised with exposure to morphine sulfate. Mice were implanted subcutaneously with 8-, 25-, or 75-mg morphine sulfate pellets. Placebo pellets of identical makeup to the 75-mg morphine pellet (without morphine of course) were used as a control. Twenty-four hours after implantation of a 75-mg morphine pellet, blood levels reached a peak of 1610 ng/ml. Corticosterone increased in parallel with morphine and reached a peak level of 966 ng/ml 24 hr after implantation. The dose response of morphine to increase corticosterone, however, was flat. The weight of the lymphoid organs, spleen and thymus, and the liver were significantly reduced in the morphine-treated groups. Morphine treatment was associated with an increase in serum albumin, SGPT, BUN, and alkaline phosphatase indicative of hepatic damage. In contrast to increased serum proteins, the C3 component of complement was reduced in a dose-dependent manner. Leukocyte number in the peripheral blood was significantly reduced, while erythrocyte number and hematocrit were both increased. The number of B cells and T cells was decreased in morphine-treated animals. However, the percentage of T cells relative to B cells was increased. The primary IgM antibody response to the T-dependent antigen, sheep red blood cells, was decreased. Natural killer cell activity was reduced in response to morphine, as was the phagocytic capacity of Kupffer cells. Host-resistance models of Listeria monocytogenes or Streptococcus pneumoniae showed an increased resistance following administration of morphine. This increased host resistance, however, was not due to an increase in antimicrobial action of sera obtained from mice treated with morphine. The majority of morphine's effects on the immune system exhibited a flat dose response, suggesting that these effects may be mediated secondarily through corticosterone.
本研究旨在调查一些可能因暴露于硫酸吗啡而受损的免疫参数。将小鼠皮下植入8毫克、25毫克或75毫克的硫酸吗啡丸剂。使用与75毫克吗啡丸剂组成相同的安慰剂丸剂（当然不含吗啡）作为对照。植入75毫克吗啡丸剂24小时后，血液水平达到峰值1610纳克/毫升。皮质酮与吗啡平行增加，植入后24小时达到峰值水平966纳克/毫升。然而，吗啡增加皮质酮的剂量反应呈平稳状态。吗啡治疗组的淋巴器官、脾脏和胸腺以及肝脏的重量显著减轻。吗啡治疗与血清白蛋白、谷丙转氨酶、尿素氮和碱性磷酸酶升高有关，提示肝损伤。与血清蛋白增加相反，补体C3成分呈剂量依赖性降低。外周血白细胞数量显著减少，而红细胞数量和血细胞比容均增加。吗啡治疗的动物中B细胞和T细胞数量减少。然而，T细胞相对于B细胞的百分比增加。对T细胞依赖性抗原绵羊红细胞的初次IgM抗体反应降低。吗啡处理后自然杀伤细胞活性降低，库普弗细胞的吞噬能力也降低。单核细胞增生李斯特菌或肺炎链球菌的宿主抗性模型显示，给予吗啡后抗性增加。然而，这种宿主抗性增加并非由于从吗啡处理的小鼠获得的血清抗菌作用增强。吗啡对免疫系统的大多数影响呈现平稳的剂量反应，表明这些影响可能继发于皮质酮介导。
