NITRIC-OXIDE AND INFLAMMATORY JOINT DISEA SES

Nitric oxide (NO) has been shown to be a major messenger molecule for regulation of vascular tone, platelet aggregation, neuronal signal tra nsduction, and immune response. NO is synthesized from L-arginine by t he NO synthases. So far, three NO synthase isoenzymes have been identi fied: two constitutive NO synthases, responsible for homoeostatic card iovascular and neuronal functions of NO, and an inducible NO synthase. After induction by certain cytokines or lipopolysaccharide this isofo rm produces large quantities of NO with cyto- and bacteriotoxic effect s. NO, synthesized by the inducible NO synthase in e.g. monocytes/macr ophages, synoviocytes or chondrocytes, plays an important role in infl ammatory joint diseases. This is documented by animal experiments and human studies in patients with rheumatoid arthritis, spondyloarthropat hies and systemic lupus erythematosus. In experimental arthritis admin istration of NO synthase inhibitors profoundly reduced disease activit y. In humans beneficial effects of NO synthesis inhibition are indicat ed indirectly: glucocorticoids, inhibiting induction of the inducible NO synthase, reduce enhanced NO synthesis and disease activity. Inhibi tion of NO synthesis is a new experimental therapeutic approach in the treatment of inflammatory joint diseases.