del Rey Adriana, Besedovsky Hugo O
Department of Immunophysiology, Institute of Physiology and Pathophysiology, Medical Faculty, Marburg, Germany.
Neuroimmunomodulation. 2008;15(1):29-36. doi: 10.1159/000135621. Epub 2008 Jul 29.
With some exceptions, the sympathetic nervous system has often been regarded as an immunosuppressive system. However, we know now that the immunoregulatory role of the sympathetic nervous system cannot be described in such absolute terms. Indeed, sympathetic neurotransmitters can inhibit or stimulate an immune response depending on numerous variables, which include the type of adrenergic receptor involved, the kind of antigen that triggers the immune response, and the subset of immune cells affected. A most important consideration is that immune and sympathetic responses are phasic phenomena and the step of the immune response at which lymphoid and/or accessory cells are exposed to neurotransmitters, or deprived from their presence, seems decisive for the outcome. The large amount of basic research on the role that the sympathetic nervous system plays in neuroimmunomodulation has prompted studies on its pathological implications. Systemic lupus erythematosus is an autoimmune lymphoproliferative disease that has mainly been associated with a Th2 shift and increased humoral responses. Lpr/lpr mice, which express a defective Fas, are commonly used as a model of this disease, and more recently, also of the autoimmune lymphoproliferative syndrome. We have found that, besides defects in the Fas pathway, lpr/lpr mice have an altered sympathetic innervation, and that this alteration contributes to the pathogenesis of the disease. The results strongly support the hypothesis that the sympathetic nervous system can modulate the expression of autoimmune lymphoproliferative diseases.
除了一些例外情况，交感神经系统常常被视为一个免疫抑制系统。然而，我们现在知道，交感神经系统的免疫调节作用不能用如此绝对的术语来描述。事实上，交感神经递质可以根据众多变量抑制或刺激免疫反应，这些变量包括所涉及的肾上腺素能受体类型、触发免疫反应的抗原种类以及受影响的免疫细胞亚群。一个最重要的考虑因素是，免疫反应和交感反应是阶段性现象，淋巴细胞和/或辅助细胞接触神经递质或缺乏神经递质的免疫反应阶段，似乎对结果起决定性作用。关于交感神经系统在神经免疫调节中所起作用的大量基础研究，促使了对其病理影响的研究。系统性红斑狼疮是一种自身免疫性淋巴细胞增生性疾病，主要与Th2偏移和体液反应增加有关。表达缺陷型Fas的Lpr/lpr小鼠通常被用作这种疾病的模型，最近也被用作自身免疫性淋巴细胞增生综合征的模型。我们发现，除了Fas途径存在缺陷外，Lpr/lpr小鼠的交感神经支配也发生了改变，并且这种改变促成了疾病的发病机制。这些结果有力地支持了交感神经系统可以调节自身免疫性淋巴细胞增生性疾病表达的假说。
