Neuroendocrinology of autoimmunity.

The HPA axis is fundamental for long-term survival and protection from the ravages of autoimmune disease. Continuing investigations suggest that the hypothesis linking susceptibility to autoimmune disease and a hyporesponsive HPA axis is somewhat simplistic. Instead, data from a number of different human diseases and from preclinical studies in a variety of models have suggested a more complicated picture. Alterations in the diurnal rhythms of ACTH, cortisol, and immune parameters appear to be linked to severity of disease. The use of low doses of steroids timed to target disrupted diurnal immune system changes in patients with RA may reduce the unfortunate side effects of long-term steroid use. Studies in cancer patients have related alterations in diurnal cortisol to survival. Whether differences in individual cortisol profiles are predictive of a deterioration in symptoms of autoimmune disease remains to be established. Responsiveness of the HPA axis to subtle challenges such as the dexamethasone suppression test and the related dexamethasone-CRF test suggest that there are different sub-populations of patients with RA and MS and these may have confounded earlier, apparently contradictory, studies. These different responses may be related to the severity of the disease. That these HPA axis differences can be altered beneficially through the use of antidepressants, as has been shown in MS, may impact on future health care strategies. However, reports of negative developments in arthritis associated with SSRI use suggest that the SSRIs may be unsuitable under some circumstances. The link of behavioral differences to alterations in neurotransmitter changes associated with disease is intriguing and opens new avenues of research. These future studies will require input from neuroscientists, neuroendocrinologists, psychologists, and immunologists working with the clinical specialties already involved in treating patients with autoimmune disease. These multidisciplinary studies reflecting the increased importance of hormonal and neurotransmitter involvement with the immune system hold great promise for the future.