Neuro-endocrine-immune axis in human rheumatoid arthritis.
We present an overview of the role of neuro-endocrine-immune mechanisms in the pathophysiological responses of patients with rheumatoid arthritis (RA). In patients with RA, proinflammatory cytokines secreted by synovial cells provoke local inflammation in the joints and, simultaneously, initiate a systemic acute phase response. Thus, profound changes of the neuro-endocrine-immune axis could take place in the patients. Defects in the hypothalamus-pituitary-adrenal axis have been observed in patients with RA. Prolactin levels are often elevated and abnormal sex hormone levels have been described in RA patients. Defective neural regulation of inflammation involving neuropeptides at least partly plays a pathogenic role in RA. We and others have found that participants of the neuro-endocrine-immune interactions, such as hormones, neurotransmitters and neuropeptides, modulate RA synovial cell functions and that they are actually produced by, and their receptors are expressed on, cells within the inflammatory joint compartment. Thus, neuropeptides and hormones not only affect a systemic acute phase response of RA patients, but also modulate local inflammation directly in RA joints. These results suggest that defects in regulatory processes which are fundamental to RA may lie in the immune system, the nervous system, the endocrine system or the interactions of these. A better understanding of neuro-endocrine-immune interactions holds the promise of new approaches to the treatment of RA with the use of hormones, neurotransmitters, neuropeptides and/or their antagonists.