Urocortin expression in synovium of patients with rheumatoid arthritis andosteoarthritis: Relation to inflammatory activity

Peripherally produced CRH acts as a local auto/paracrine proinflammatory ag ent. Urocortin is a new member of the CRH family that acts through the fami ly of CRH receptors. In this study, we demonstrated that the expression of urocortin mRNA in synovia of patients with rheumatoid arthritis was greater than that of patients with osteoarthritis. Also, we detected urocortin and CRH receptor immunoreactivity in the synovial lining cell layer, subsynovi al stromal cells, blood vessel endothelial cells, and mononuclear inflammat ory cells from the joints of rheumatoid arthritis and osteoarthritis patien ts. The expression of immunoreactive urocortin was significantly greater in rheumatoid arthritis than ostcoarthritis (P<0.0001) and correlated with th e extent of inflammatory infiltrate. CRH receptor immunoreactivity was stro ng in mononuclear inflammatory cells of rheumatoid arthritis synovia. Uroco rtin stimulated <beta>IL-1 and IL-6 secretion by human peripheral blood mon onuclear cells in vitro. These findings suggest that, like CRH, urocortin i s present in peripheral inflammatory sites, such as rheumatoid synovium, an d acts as an immune-inflammatory mediator.