Straub Rainer H
Laboratory of Experimental Rheumatology and Neuroendocrino-Immunology, Department of Internal Medicine I, University Hospital Regensburg, 93042 Regensburg, Germany.
Brain Behav Immun. 2007 Jul;21(5):528-34. doi: 10.1016/j.bbi.2007.04.005. Epub 2007 May 22.
In the decades before 1987, most of the research devoted to neuronal innervation was carried out in primary and secondary lymphoid organs at very different locations. This was an important period in order to understand hard-wiring of immune organs in physiology. Between 1988 and 1997, with the appearance of specific antibodies against neuronal markers, innervation was studied in inflamed tissue of patients and of animals with autoimmune diseases. This period clearly revealed that nerve fibers of, both, the sympathetic and sensory nervous system are altered, but only small amounts of tissue have been investigated by qualitative but not quantitative techniques. Between 1998 and 2007, with the understanding that sympathetic and sensory neurotransmitters might play opposite roles in inflammation, nerve fibers of the different nervous systems have been studied in parallel using quantitative techniques. These studies have been carried out in a large number of patients with long-standing autoimmune diseases. It turned out that sympathetic nerve fibers are lost in chronically inflamed tissue, while substance P-positive nerve fibers sprout into the inflamed area. This might be important because high concentrations of sympathetic neurotransmitters are antiinflammatory whereas substance P has a proinflammatory role. The first challenge for future research is the determination of innervation in the early human autoimmune disease. The second challenge is the identification of reasons for the differential loss of sympathetic in relation to sensory nerve fibers. It might well be that nerve repellent factors specific for the sympathetic nerve fiber might play an important role for the observed differential loss. Whether, or not, a therapy can be based on these findings remains to be established.
在1987年之前的几十年里，大多数关于神经元支配的研究是在位置截然不同的初级和次级淋巴器官中进行的。这是了解免疫器官在生理学上的硬连接的一个重要时期。1988年至1997年间，随着针对神经元标记物的特异性抗体的出现，人们对患有自身免疫性疾病的患者和动物的炎症组织中的神经支配进行了研究。这一时期清楚地表明，交感神经系统和感觉神经系统的神经纤维都发生了改变，但仅用定性而非定量技术对少量组织进行了研究。1998年至2007年间，随着人们认识到交感神经递质和感觉神经递质在炎症中可能发挥相反的作用，不同神经系统的神经纤维开始使用定量技术进行平行研究。这些研究是在大量患有长期自身免疫性疾病的患者中进行的。结果发现，交感神经纤维在慢性炎症组织中丢失，而P物质阳性神经纤维则向炎症区域生长。这可能很重要，因为高浓度的交感神经递质具有抗炎作用，而P物质具有促炎作用。未来研究的第一个挑战是确定人类早期自身免疫性疾病中的神经支配情况。第二个挑战是确定交感神经纤维与感觉神经纤维差异丢失的原因。很可能是交感神经纤维特有的神经排斥因子对观察到的差异丢失起了重要作用。基于这些发现是否能够进行治疗仍有待确定。
