Augmented production of proinflammatory cytokines and accelerated allotransplantation reactions in heroin-treated mice
Augmented production of proinflammatory cytokines and accelerated allotransplantation reactions in heroin-treated mice
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DOI：
10.1046/j.1365-2249.2003.02103.x
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发表时间：
2003-04-01
影响因子：
4.6
通讯作者：
Wilczek, H
中科院分区：
文献类型：
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作者：
Holán, V;Zajícová, A;Wilczek, H
海洛因治疗或滥用药物成瘾影响许多生理功能，包括免疫系统的反应。虽然海洛因（或吗啡）给药后免疫系统的各种表现的抑制已被报道，我们在这里表明，促炎细胞因子和一氧化氮（NO）的产生增强和同种异体移植反应加速海洛因治疗的受者显着。小鼠通过皮下注射海洛因（二乙酰吗啡）进行治疗，每日一次或多次给药。检测了经处理小鼠的脾细胞在体外对同种异体抗原的应答和产生IL-2、IL-4、IL-10和IFN-γ的能力，以及腹腔巨噬细胞产生IL-1 β、IL-12和NO的能力。海洛因给药后2 h内，对同种抗原的增殖反应和IL-1 β、IFN-γ、IL-12和NO的产生显著增强。相反，抗炎细胞因子IL-4和IL-10的产生同时相当减少。因此，海洛因治疗小鼠的皮肤移植物比未治疗或载体治疗的受体更迅速地被排斥。同样，在海洛因处理的小鼠中，高剂量肿瘤细胞诱导的同种异体肿瘤的生长受到显著抑制。海洛因对促炎细胞因子产生的增强作用可被经典阿片受体特异性抑制剂纳洛酮所拮抗。这些结果表明，海洛因治疗增加了促炎细胞因子的产生，加速了同种异体移植反应。因此，这些观察结果说明了海洛因对免疫系统影响的复杂性，在对阿片剂成瘾者进行药物治疗和在各种临床情况下使用吗啡减轻疼痛时应考虑到这一点。
Heroin treatment or abusive drug addiction influences many physiological functions, including the reactions of the immune system. Although suppression of various manifestations of the immune system after heroin (or morphine) administration has been reported, we show here that production of proinflammatory cytokines and nitric oxide (NO) was enhanced and allotransplantation reactions were accelerated significantly in heroin-treated recipients. Mice were treated by a subcutaneous administration of heroin (diacetylmorphine) given in one or repeated daily doses. The ability of spleen cells from treated mice to respond in vitro to alloantigens and to produce IL-2, IL-4, IL-10 and IFN-gamma, and the production of IL-1beta, IL-12 and NO by peritoneal macrophages, were tested. Within 2 h after heroin administration, proliferative responses to alloantigens and the production of IL-1beta, IFN-gamma, IL-12 and NO were enhanced significantly. In contrast, the production of anti-inflammatory cytokines IL-4 and IL-10 was at the same time rather decreased. As a consequence, skin allografts in heroin-treated mice were rejected more promptly than in untreated or vehicle-treated recipients. Similarly, the growth of allogeneic tumours induced by high doses of tumour cells was suppressed significantly in heroin-treated mice. The enhancing effects of heroin on the production of proinflammatory cytokines were antagonized by naltrexone, a specific inhibitor of classic opioid receptors. These results show that heroin treatment augments production of proinflammatory cytokines and accelerates allotransplantation reactions. The observations thus illustrate the complexity of the effects of heroin on the immune system and should be taken into account during medical treatment of opiate addicts and in the use of morphine to decrease pain in various clinical situations.