Morphine suppresses primary humoral immune responses by a predominantly indirect mechanism.
Morphine suppresses primary humoral immune responses by a predominantly indirect mechanism.
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发表时间：
1992-09
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通讯作者：
S. Pruett;Y. Han;B. Fuchs
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作者：
S. Pruett;Y. Han;B. Fuchs
在动物模型中，吗啡抑制体液免疫应答，导致胸腺发育不全并抑制NK（自然杀伤细胞）活性。有证据表明，胸腺发育不全和NK抑制主要由间接机制介导。吗啡诱导的体液免疫抑制机制尚不确定。最近的报告表明，吗啡和其他阿片类药物可以直接作用于免疫系统的细胞，以抑制Mishell-Dutton培养物中抗体形成细胞（AFC）的产生。本研究旨在评估吗啡诱导的体液免疫抑制的直接和间接机制的作用。来自经皮下注射吗啡处理的小鼠的脾细胞。在Mishell-Dutton培养物中植入缓释75 mg丸粒功能障碍。暴露于吗啡在体内12或24小时造成显着抑制AFC生产刺激绵羊红细胞在Mishell-Dutton文化。相比之下，在各种条件下直接添加吗啡或κ选择性阿片受体激动剂U 50，488 H到Mishell-Dutton培养物中对AFC产生的影响很小或没有影响。这些结果表明，吗啡对体液反应的抑制主要不是由吗啡对免疫系统的直接作用介导的。通过使用糖皮质激素拮抗剂RU 38486治疗小鼠，体内给予吗啡抑制AFC反应基本上被阻断，表明糖皮质激素可能参与吗啡引起脾细胞功能障碍的间接机制。
Morphine suppresses humoral immune responses, causes thymic hypoplasia and suppresses NK (natural killer) activity in animal models. There is evidence that thymic hypoplasia and NK suppression are predominantly mediated by indirect mechanisms. The mechanism of morphine-induced humoral immunosuppression is less certain. Recent reports suggest that morphine and other opioids can directly act on cells of the immune system to suppress the generation of antibody-forming cells (AFC) in Mishell-Dutton cultures. The present study was designed to assess the roles of direct and indirect mechanisms in morphine-induced suppression of humoral immunity. Splenocytes from mice treated with morphine by s.c. implantation of a slow-release 75 mg pellet were dysfunctional in Mishell-Dutton cultures. Exposure to morphine in vivo for 12 or 24 hr caused significant suppression of the AFC production stimulated by sheep erythrocytes in Mishell-Dutton cultures. In contrast, direct addition of morphine or the kappa selective opioid agonist U50,488H to Mishell-Dutton cultures under a variety of conditions had little or no effect on AFC generation. These results indicate that suppression of humoral responses by morphine is not primarily mediated by direct action of morphine on the immune system. Suppression of AFC responses by administration of morphine in vivo was substantially blocked by treating mice with the glucocorticoid antagonist RU 38486, suggesting that glucocorticoids may be involved in the indirect mechanism by which morphine causes splenocyte dysfunction.