Interactions of autonomic nervous, neuroendocrine, and immune systems in rheumatoid arthritis.
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.
Baerwald
C G
CG
Department of Rheumatology, University Hospital, Medical Clinic and Polyclinic IV, Leipzig, Germany.
Burmester
G R
GR
Krause
A
A
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000503:physiopathology*; D001341:Autonomic Nervous System / Q000502:physiology*; D002395:Catecholamines / Q000494:pharmacology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007107:Immune System / Q000502:physiology*; D009490:Neurosecretory Systems / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000502:physiology; D011941:Receptors, Adrenergic / Q000502:physiology
D002395:Catecholamines; D011941:Receptors, Adrenergic