Nitric oxide and inflammatory joint diseases

Nitric oxide (NO) has been shown to be a major messenger molecule for regulation of vascular tone, platelet aggregation, neuronal signal transduction, and immune response. NO is synthesized from L-arginine by the NO synthases. So far, three NO synthase isoenzymes have been identified: two constitutive NO synthases, responsible for homoeostatic cardiovascular and neuronal functions of NO, and an inducible NO synthase. After induction by certain cytokines or lipopolysaccharide this isoform produces large quantities of NO with cyto- and bacteriotoxic effects. NO, synthesized by the inducible NO synthase in e.g. monocytes/macrophages, synoviocytes or chondrocytes, plays an important role in inflammatory joint diseases. This is documented by animal experiments and human studies in patients with rheumatoid arthritis, spondyloarthropathies and systemic lupus erythematosus. In experimental arthritis administration of NO synthase inhibitors profoundly reduced disease activity. In humans beneficial effects of NO synthesis inhibition are indicated indirectly: glucocorticoids, inhibiting induction of the inducible NO synthase, reduce enhanced NO synthesis and disease activity. Inhibition of NO synthesis is a new experimental therapeutic approach in the treatment of inflammatory joint diseases.