Nitric oxide and inflammatory joint diseases

Nitric oxide (NO) is synthesized from L-arginine by the NO synthases. At present, mainly three NO synthase isoenzyme groups are differentiated: two constitutive NO synthases, responsible for homeostatic cardiovascular and neuronal functions of NO, and an inducible NO synthase. After induction by certain cytokines or endotoxin, this latter isoform produces large quantities of NO with cyto- and bacteriotoxic effects. High amounts of NO, synthesized systemically and intra-articularly, play an important role in inflammatory joint diseases, as shown in animal models of arthritis and in patients with rheumatoid arthritis or spondyloarthropathies. In experimental arthritis, administration of NO synthase inhibitors profoundly reduced disease activity. In humans, beneficial effects of NO synthesis inhibition are inferred from indirect evidence: glucocorticoids, inhibiting induction of the inducible NO synthase, reduce enhanced NO synthesis and disease activity. Thus, selective inhibition of the pathologically enhanced NO synthesis emerges as a new experimental therapeutic approach in the treatment of inflammatory joint diseases.