Animal model studies from our lab have indicated that neuroendocrine mechanisms play a major role in regulating inflammatory processes that are operative in chronic proliferative forms of arthritis. We are actively exploring these concepts in patients with rheumatoid arthritis (RA). We have demonstrated high levels of expression of corticotropin releasing hormone (CRH) in synovial fluids and tissues from patients with RA. We have also demonstrated that cyclooxygenase -1 and -2 are both expressed in rheumatoid synovia, but only Cox-2 is inducible. Interleukin-1 and PMA are potent stimulators of Cox-2, but not Cox-1. Corticosteroids suppress Cox-2, but not Cox-1 expression. These data support the view that Cox-2, like CRH, may mediate signals between the neuroendocrine and inflammatory systems. Dysregulated expression of the polypeptides appears to be associated with inflammatory joint disease.
