Corticotropin-releasing hormone in synovial fluids and tissues of patients with rheumatoid arthritis and osteoarthritis.

Crofford LJ, Sano H, Karalis K, Friedman TC, Epps HR, Remmers EF, Mathern P, Chrousos GP, Wilder RL
J Immunol. 1993 151 (3): 1587-96

PMID: 8335947

Inflammation normally results in enhanced synthesis and secretion of hypothalamic corticotropin-releasing hormone (CRH) which, in turn, exerts antiinflammatory effects by virtue of increased adrenal glucocorticoid production. CRH and CRH binding sites are also expressed in the peripheral nervous and immune systems. Our groups have recently shown that CRH is secreted locally in acute carrageenin-induced inflammation in rats and has predominantly proinflammatory effects. We have also shown that CRH is expressed in the joints of Lewis rats with experimental arthritis. To determine if CRH is present in human inflammatory arthritis, we examined synovial fluids and tissues from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) and normal individuals. We found markedly enhanced expression of immunoreactive CRH in situ in synovium from patients, which was significantly greater in RA than in OA (p < 0.01). CRH concentrations were also significantly higher in RA (140 +/- 33 pg/ml, mean +/- SEM; n = 10) than OA (25 +/- 4 pg/ml; n = 6) synovial fluids (p < 0.005). HPLC showed immunoreactive CRH extracted from RA and OA synovial tissues and fluids coeluted with CRH 1-41. CRH mRNA was present in low levels in synovial tissue from patients with RA and, to a lesser extent, OA. In summary, immunoreactive CRH is locally secreted in the synovium of patients with RA and, at lower levels, OA. These data support the view that CRH functions as an autocrine and/or paracrine mediator of inflammation in humans.

MeSH Terms (13)

Arthritis, Rheumatoid Base Sequence Chromatography, High Pressure Liquid Corticotropin-Releasing Hormone Gene Expression Humans Immunoenzyme Techniques Molecular Sequence Data Oligodeoxyribonucleotides Osteoarthritis Polymerase Chain Reaction RNA, Messenger Synovial Fluid

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