Stefano G B, Leung M K, Bilfinger T V, Scharrer B
Multidisciplinary Center for the Study of Aging, Old Westbury Neuroscience Research Institute, State University of New York 11568, USA.
J Neuroimmunol. 1995 Dec 31;63(2):175-81. doi: 10.1016/0165-5728(95)00147-6.
This study deals with a novel role of morphine in the modulation of cellular responsiveness to immunostimulatory substances that, at first glance, appears to be in contrast to the well documented immunoinhibitory short-term effects of opiate alkaloids on cells simultaneously exposed to stimulatory molecules. Vertebrate and invertebrate immunocytes pre-exposed to morphine (10(-6) M) in vitro for at least 24 h prior to the administration of lipopolysaccharide (LPS; 1.0 micrograms/ml) or other immunoactivating substances have revealed a distinct enhancement of their responsiveness to these signals, e.g. monocytes exposed to LPS alone resulted in 21% activation, whereas the morphine pretreated level was at 40% (P < 0.01). Prolonged pretreatment with morphine of naive human monocytes had the same effect on their sensitivity to plasma from patients having undergone cardiopulmonary bypass (CPB) operations followed by a diffuse inflammatory response. These results suggest that endogenous opiates may participate, in more than one way, in re-establishing an organism's readiness to meet a new demand on its immune system. Additional support for the concept of a role of endogenous opiates in immunomodulation was obtained by the results of in vivo tests with experimentally induced stress in Mytilus. Following their stress-induced stimulation, these animals' immunocytes could be shown to become exposed for some time to a measurable rise in endogenous morphine-like material (9 pmol/ml increasing to 59). These immunocytes, like those preincubated with exogenous morphine, displayed a heightened sensitivity to stimulation by LPS (control 21.3 +/- 3.1% activation compared to 47.2 +/- 5.1) when the morphine levels dropped. The mechanism of this enhancement of responsiveness to immunostimulation following the prolonged exposure of immunocytes to morphine, and its relationship with the known short-term immunoinhibitory opiate effects on the immune system, remains to be ascertained.
本研究探讨了吗啡在调节细胞对免疫刺激物质反应性方面的新作用，乍一看，这似乎与阿片生物碱对同时暴露于刺激分子的细胞具有充分记录的免疫抑制短期效应形成对比。在体外预先将脊椎动物和无脊椎动物免疫细胞暴露于吗啡（10⁻⁶ M）至少24小时，然后再给予脂多糖（LPS；1.0微克/毫升）或其他免疫激活物质，结果显示这些细胞对这些信号的反应性明显增强，例如，单独暴露于LPS的单核细胞激活率为21%，而经吗啡预处理后的激活率为40%（P < 0.01）。用吗啡对未接触过的人类单核细胞进行长时间预处理，对其对经历体外循环（CPB）手术并伴有弥漫性炎症反应患者血浆的敏感性有相同影响。这些结果表明，内源性阿片类物质可能以多种方式参与重新建立机体应对免疫系统新需求的准备状态。通过对贻贝进行实验性诱导应激的体内试验结果，进一步支持了内源性阿片类物质在免疫调节中起作用的概念。在应激诱导刺激后，这些动物的免疫细胞可显示在一段时间内暴露于内源性吗啡样物质的可测量升高（从9皮摩尔/毫升增加到59）。当吗啡水平下降时，这些免疫细胞与用外源性吗啡预孵育的细胞一样，对LPS刺激表现出更高的敏感性（对照组激活率为21.3±3.1%，而处理组为47.2±5.1）。免疫细胞长时间暴露于吗啡后对免疫刺激反应性增强的机制，及其与已知阿片类物质对免疫系统的短期免疫抑制作用的关系，仍有待确定。
