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Recent Advances in Neuro-Endocrine-Immune Interactions in the Pathophysiology of Rheumatoid Arthritis

[ Vol. 2 , Issue. 2 ]


Hideshi Yoshikawa, Kazuhiko Nara and Noboru Suzuki   Pages 191 - 205 ( 15 )


Rheumatoid arthritis (RA) is an autoimmune disorder resulting from the combination of several predisposing factors, including hormonal influences and immune responses. Stress response system, including hypothalamic-pituitaryadrenal/ gonadal axes and sympathetic nervous system plays important roles for its pathophysiology. Proinflammatory cytokines secreted by synovial cells and activation of inflammatory cells provoke systemic as well as local inflammatory stresses in RA. However, the decreased secretion of adrenal androgens and gonadal testosterone, and the decreased number of sympathetic nerve fibers (norepinephrine) in the synovial tissue are observed in RA, and eventually leading to the Th1 dominant immune aberration. These suggest a loss of the stress-induced feedback regulation in endocrineimmune and neuro-immune interactions, leading to acceleration of chronic inflammation in RA. The local nociceptive input and sensitization of corresponding segments of spinal cord, resulted in continuous pain with stabilization of afferent sensory fibers and continuous release of proinflammatory neuropeptides, including substance P. Thus, inappropriate secretion of hormones and neuropeptides contributes to vicious cycle in progression of inflammatory responses. In this review, we discuss the recent advances of immunological aberrations and neuro-endocrine-immune interactions in pathophysiology of RA.


HPA axis, prolactin, gonadal hormones, sympathetic nervous system, neuropeptides, rheumatoid arthritis


Departments of Immunologyand Medicine, St. Marianna University School of Medicine, 2-16-1, Sugao,Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan.

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