CORTICOTROPIN-RELEASING HORMONE IN SYNOVIAL-FLUIDS AND TISSUES OF PATIENTS WITH RHEUMATOID-ARTHRITIS AND OSTEOARTHRITIS

Inflammation normally results in enhanced synthesis and secretion of h ypothalamic corticotropin releasing hormone (CRH) which, in turn, exer ts antiinflammatory effects by virtue of increased adrenal glucocortic oid production. CRH and CRH binding sites are also expressed in the pe ripheral nervous and immune systems. Our groups have recently shown th at CRH is secreted locally in acute carrageenin-induced inflammation i n rats and has predominantly proinflammatory effects. We have also sho wn that CRH is expressed in the joints of Lewis rats with experimental arthritis. To determine if CRH is present in human inflammatory arthr itis, we examined synovial fluids and tissues from patients with rheum atoid arthritis (RA) or osteoarthritis (OA) and normal individuals. We found markedly enhanced expression of immunoreactive CRH in situ in s ynovium from patients, which was significantly greater in RA than in O A (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 extract ed 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 wi th RA and, to a lesser extent, OA. In summary, immunoreactive CRH is l ocally secreted in the synovium of patients with RA and, at lower leve ls, OA. These data support the view that CRH functions as an autocrine and/or paracrine mediator of inflammation in humans.