Cross R J, Jackson J C, Brooks W H, Sparks D L, Markesbery W R, Roszman T L
Immunology. 1986 Jan;57(1):145-52.
Previous studies from this laboratory and others show that perturbations of the central nervous system modulate immune function. In addition, reports from several investigators indicate that depletion of the neurotransmitter norepinephrine (NE) in peripheral nerves by injecting the neurotoxin 6-hydroxydopamine (6-OHDA), can enhance or suppress the antibody response. However, immunocompetence following brain depletion of catecholamines has not been investigated. In this study, we investigated the effects of injecting 6-OHDA into the cisterna magna of male CBA/J mice, and determined the effects of this treatment on both the IgM and IgG antibody responses to sheep red blood cells (SRBC). Both responses are suppressed compared to saline-injected control or normal animals. Animals treated with 6-OHDA have decreased levels of NE in the midbrain, pons-medulla and hypothalamus, while dopamine levels did not change in these brain regions but was decreased in the striatum. The percentage of splenic T cells and B cells was not affected by 6-OHDA treatment. Although there is a marked increase in plasma corticosterone levels in 6-OHDA-treated mice, saline-injected control animals have equivalent increases in plasma corticosterone without concomitant impairment of the immune response. Thus, the decline in immune responsiveness following 6-OHDA treatment does not result from corticosterone-induced immunosuppression. Analysis of the kinetics of the primary IgG response following 6-OHDA treatment indicates that the magnitude, but not the kinetics, of the response decreases. Experiments to determine the effects of 6-OHDA on the afferent and efferent phrases of the response demonstrate that it is effective only when administered prior to immunization, and thus must inhibit early events involved in the initiation of the response. Additional experiments show that mice can be immunized 2 weeks following brain catecholamines depletion and still exhibit a decreased antibody response. However, the response returns to normal levels if immunization is delayed 4 weeks after injection. Further experiments demonstrated that 6-OHDA treatment has no effect on the secondary antibody response, but does inhibit the development of immunological memory. Collectively, these results indicate that 6-OHDA treatment has a profound inhibitory effect on the induction of the primary antibody response and immunological memory development, but is without effect on the secondary antibody response. The data further substantiate the existence of a link between the brain and the immune response.
本实验室及其他机构之前的研究表明，中枢神经系统的扰动会调节免疫功能。此外，几位研究人员的报告指出，通过注射神经毒素6-羟基多巴胺（6-OHDA）来耗尽外周神经中的神经递质去甲肾上腺素（NE），可增强或抑制抗体反应。然而，脑内儿茶酚胺耗尽后的免疫能力尚未得到研究。在本研究中，我们研究了向雄性CBA/J小鼠的脑池中注射6-OHDA的效果，并确定了这种处理对针对绵羊红细胞（SRBC）的IgM和IgG抗体反应的影响。与注射生理盐水的对照动物或正常动物相比，这两种反应均受到抑制。用6-OHDA处理的动物中脑、脑桥-延髓和下丘脑的NE水平降低，而这些脑区的多巴胺水平没有变化，但纹状体中的多巴胺水平降低。脾脏T细胞和B细胞的百分比不受6-OHDA处理的影响。虽然6-OHDA处理的小鼠血浆皮质酮水平显著升高，但注射生理盐水的对照动物血浆皮质酮也有同等程度的升高，且免疫反应并未随之受损。因此，6-OHDA处理后免疫反应性的下降并非由皮质酮诱导的免疫抑制所致。对6-OHDA处理后初次IgG反应动力学的分析表明，反应的幅度而非动力学有所降低。确定6-OHDA对反应的传入和传出阶段影响的实验表明，它仅在免疫前给药时有效，因此必定抑制了反应启动过程中涉及的早期事件。额外的实验表明，小鼠在脑儿茶酚胺耗尽后2周可以进行免疫，但抗体反应仍会降低。然而，如果在注射后4周延迟免疫，反应会恢复到正常水平。进一步的实验表明，6-OHDA处理对二次抗体反应没有影响，但会抑制免疫记忆的形成。总体而言，这些结果表明，6-OHDA处理对初次抗体反应的诱导和免疫记忆的形成具有深远的抑制作用，但对二次抗体反应没有影响。这些数据进一步证实了大脑与免疫反应之间存在联系。
