Baerwald C G, Burmester G R, Krause A
Department of Rheumatology, University Hospital, Medical Clinic and Polyclinic IV, Leipzig, Germany.
Rheum Dis Clin North Am. 2000 Nov;26(4):841-57. doi: 10.1016/s0889-857x(05)70172-1.
In general, it is assumed that the two pathways (i.e., HPA axis and sympathetic nervous system) probably act cooperatively to maintain homeostasis. The previously mentioned studies clearly point to a disturbance in the interaction between the ANS, the HPA axis, and the immune system in chronic rheumatic diseases (Fig. 2). Even early on in the course of RA, these changes can be observed. Along with the results obtained in animal models, an important role of neuroendocrine interactions in the pathogenesis of RA is proposed. Further studies are required to establish the exact contribution of the ANS in the initiation and perpetuation of RA. To date, it is quite obvious that neuropeptides play a part in the orchestration of the various molecules (e.g., cytokines) exerting modulatory effects on immune cells. One can speculate that therapeutic implications are likely to result from investigations on the ANS-immune interactions. Based on early observations that blocking catecholamine actions ameliorate symptoms of RA, it is quite promising to follow this avenue in investigating ANS-immune interactions of various time points of the disease. Conversely, further studies are required to determine the contribution of the HPA axis to the onset of RA. Results from ongoing studies are eagerly awaited so as to establish new therapeutic options. In the future,it may be possible to interfere with the inflammatory process in RA by an exactly timed neuroendocrine intervention right at or even before the onset of disease. Therapy with steroids in RA might be better planned based on the genetically determined reactivity of an individual's HPA axis. In this respect, a recent report by Masi et al is of special interest. Based on the current literature on the disturbances in the neuroendocrine, immune, and microvascular systems found in early RA, the authors hypothesize that an imbalance in the interactive homeostasis of these systems develops during a long preclinical phase and eventually leads to the outbreak of the disease in genetically predisposed individuals. This interesting hypothesis includes the perspective that individuals prone to develop RA may be identified in a preclinical phase and treated prophylactically. In any event, results from all these studies are promising in two ways: to gain more insight in the pathogenic process of RA and to establish novel therapies to help the patients bear their burden of a chronic rheumatic disease.
一般而言，假定两条途径（即下丘脑-垂体-肾上腺轴和交感神经系统）可能协同作用以维持体内平衡。前述研究清楚地表明，在慢性风湿性疾病中，自主神经系统、下丘脑-垂体-肾上腺轴和免疫系统之间的相互作用存在紊乱（图2）。甚至在类风湿关节炎病程的早期，就能观察到这些变化。结合在动物模型中获得的结果，提示神经内分泌相互作用在类风湿关节炎发病机制中起重要作用。需要进一步研究以确定自主神经系统在类风湿关节炎的起始和持续过程中的确切作用。迄今为止，很明显神经肽在协调对免疫细胞发挥调节作用的各种分子（如细胞因子）中发挥作用。可以推测，对自主神经-免疫相互作用的研究可能会产生治疗意义。基于早期观察结果，即阻断儿茶酚胺作用可改善类风湿关节炎症状，沿着这条途径研究疾病不同时间点的自主神经-免疫相互作用很有前景。相反，需要进一步研究以确定下丘脑-垂体-肾上腺轴对类风湿关节炎发病的作用。人们急切期待正在进行的研究结果，以便确立新的治疗选择。未来，有可能在疾病发作时甚至在疾病发作之前，通过精确适时的神经内分泌干预来干扰类风湿关节炎的炎症过程。基于个体下丘脑-垂体-肾上腺轴的基因决定反应性，类风湿关节炎的类固醇治疗可能会有更好的规划。在这方面，马西等人最近的一份报告特别值得关注。基于目前关于早期类风湿关节炎中神经内分泌、免疫和微血管系统紊乱的文献，作者假设在漫长的临床前期，这些系统的交互体内平衡会出现失衡，最终导致遗传易感个体发病。这个有趣的假设包括这样一种观点，即有可能在临床前期识别出易患类风湿关节炎的个体并进行预防性治疗。无论如何，所有这些研究的结果在两个方面都很有前景：更深入了解类风湿关节炎的发病过程，并确立新的疗法以帮助患者承受慢性风湿性疾病的负担。
