OPIOID MODULATION OF IMMUNOCOMPETENCE

众所周知，海洛因成瘾者的感染率较高。 这 该提案旨在确定阿片类药物对 免疫活性 在体外水平上，研究将检查是否 阿片类药物和阿片肽可以改变T细胞应答。 阿片类药物，如 吗啡、拮抗剂如纳洛酮和阿片肽，如 β-内啡肽，甲硫氨酸-脑啡肽和亮氨酸-脑啡肽，将是 测试它们对大鼠培养物中T细胞增殖的影响 脾细胞和胸腺细胞。 [3 H]胸腺嘧啶核苷掺入DNA中 T细胞有丝分裂原的存在将被用作增殖的量度。 钙内流是与有丝分裂原相关的最早期事件之一- 刺激T细胞活化。 阿片类药物也将进行测试， 对淋巴细胞基础和丝裂原刺激的45 Ca 2+摄取的影响。 ~（125）I β-内啡肽与淋巴细胞的结合和内化 将被定性。 阿片类药物和阿片肽 将比较淋巴细胞上的阻断[125] β内啡肽结合位点 中枢神经系统中的β-内啡肽结合位点。 溶血空斑试验将用于确定阿片类药物是否可以改变 抗体合成 自然杀伤细胞毒性，通过 标准的51 Cr释放测定，将确定阿片类药物是否可以改变 细胞介导的杀伤靶细胞。 在体内水平上，这些测定法 将用于检测免疫细胞反应的变化， 吗啡依赖大鼠，与安慰剂治疗的对照组相比。 这些 研究将导致更好地了解阿片类药物如何调节 免疫能力，并可能有助于解释为什么海洛因成瘾者非常 易受病毒感染。

Heroin addicts are known to have elevated rates of infection. This proposal is directed at determining the effect of opiates on immunocompetence. On the in vitro level, studies will examine whether opiates and opioid peptides can alter T cell responses. Opiates such as morphine, antagonists such as naloxone, and opioid peptides, such as beta-endorphin, methionine-enkephalin, and leucine-enkephalin, will be tested for their effect on T cell proliferation in cultures of rat splenocytes and thymocytes. [3H)Thymidine incorporation into DNA in the presence of T cell mitogens will be used as a measure of proliferation. Calcium influx is one of the earliest events associated with mitogen- stimulated T cell activation. Opioids will also be tested for their effect on basal and mitogen-stimulated 45 Ca 2+ uptake into lymphocytes. The binding and internalization of [125I] beta-endorphin into lymphocytes will be characterized. The ability of opiates and opioid peptides to block [125] beta endorphin binding site on lymphocytes will be compared to the beta-endorphin binding site in the central nervous system. Hemolytic plaque assays will be used to determine if opioids can alter antibody synthesis. Natural killer cytotoxicity as measured by a standard 51 Cr release assay, will determine if opioids can alter the cell-mediated killing target cells. On the in vivo level, these assays will be used to detect alterations in the immunce cell responses of morphine-dependent rats, compared with placebo-treated controls. These studies will results in a better understanding of how opiates modulate immunocompetence and may help explain why heroin addicts are very susceptible to viral infection.