Stanulis E D, Jordan S D, Rosecrans J A, Holsapple M P
Department of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0613, USA.
Immunopharmacology. 1997 Aug;37(1):25-33. doi: 10.1016/s0162-3109(96)00167-1.
Cocaine has been shown to affect immune function through the release of corticosterone. Acute administration of both cocaine and corticosterone produces an enhancement of the T-dependent antibody response to sheep erythrocytes. The T-independent antibody response to DNP-ficoll is not enhanced under identical conditions, suggesting that the T-cell is involved as a cellular target. We examined T-helper cell cytokine production following in vivo cocaine administration and found an increase in IL-4 and IL-10; while IL-2 and IFN-gamma were unaffected. The rise in Th2 cytokines is consistent with an enhanced T-dependent antibody response, a measure of humoral immunity. Because previous results showed that the enhancement by cocaine is mediated via corticosterone, the direct effects of corticosterone on Th1/Th2 in vitro cytokine production were investigated. Th1 cytokines, IL-2 and IFN-gamma, were dose-dependently suppressed by corticosterone at physiologic concentrations. In contrast Th2 cytokines, IL-4 and IL-10, exhibited a biphasic dose response curve, whereby an enhancement was observed at low doses, followed by suppression at higher doses. In order to determine the consequences of this apparent shift towards a Th2 response on a Th1 response, we looked at the delayed-type hypersensitivity response to sheep erythrocytes. This measure of cell-mediated immunity was not significantly affected by acute cocaine, however, corticosterone administration resulted in a significant suppression. These results indicate that corticosterone can produce a shift towards a Th2 predominate response, possibly at the expense of Th1-mediated responses.
可卡因已被证明可通过释放皮质酮来影响免疫功能。急性给予可卡因和皮质酮均可增强对绵羊红细胞的T细胞依赖性抗体反应。在相同条件下，对二硝基苯-聚蔗糖的非T细胞依赖性抗体反应并未增强，这表明T细胞作为细胞靶点参与其中。我们检测了体内给予可卡因后T辅助细胞细胞因子的产生情况，发现白细胞介素-4（IL-4）和白细胞介素-10（IL-10）增加；而白细胞介素-2（IL-2）和干扰素-γ（IFN-γ）未受影响。Th2细胞因子的增加与增强的T细胞依赖性抗体反应一致，这是体液免疫的一种衡量指标。由于先前的结果表明可卡因的增强作用是通过皮质酮介导的，因此研究了皮质酮对体外Th1/Th2细胞因子产生的直接影响。生理浓度的皮质酮可剂量依赖性地抑制Th1细胞因子IL-2和IFN-γ。相比之下，Th2细胞因子IL-4和IL-10呈现双相剂量反应曲线，即在低剂量时观察到增强，随后在高剂量时受到抑制。为了确定这种明显向Th2反应转变对Th1反应的影响，我们观察了对绵羊红细胞的迟发型超敏反应。这种细胞介导免疫的指标未受到急性可卡因的显著影响，然而，给予皮质酮导致了显著抑制。这些结果表明，皮质酮可能会导致向以Th2为主导的反应转变，可能是以牺牲Th1介导的反应为代价。
