Nitric oxide and inflammatory joint diseases

Nitric oxide (NO) is synthesized from L-arginine by the NO synthases. Atpresent, mainly three NO synthase isoenzyme groups are differentiated: twoconstitutive NO synthases, responsible for homeostatic cardiovascular andneuronal functions of NO, and an inducible NO synthase. After induction bycertain cytokines or endotoxin, this latter isoform produces largequantities of NO with cyto- and bacteriotoxic effects. High amounts of NO,synthesized systemically and intra-articularly, play an important role ininflammatory joint diseases, as shown in animal models of arthritis and inpatients with rheumatoid arthritis or spondyloarthropathies. Inexperimental arthritis, administration of NO synthase inhibitors profoundlyreduced disease activity. In humans, beneficial effects of NO synthesisinhibition are inferred from indirect evidence: glucocorticoids, inhibitinginduction of the inducible NO synthase, reduce enhanced NO synthesis anddisease activity. Thus, selective inhibition of the pathologically enhancedNO synthesis emerges as a new experimental therapeutic approach in thetreatment of inflammatory joint diseases.