Nitric oxide and inflammatory arthritides.

Nitric oxide (NO), first identified as endothelium-derived relaxing factor (EDRF), is a free radical synthesized from L-arginine by NO synthases (NOS). NO plays vital roles in biological responses, including regulation of vascular tone, neurotransmission, anti-viral defense and immune response. There are two isoforms in NOS; constitutive NOS (cNOS) and inducible NOS (iNOS). Inflammatory cytokines such as interleukin-1(IL-1), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) induce iNOS expression in various cells including macrophages. NO production is increased in inflammatory arthritides both in rodent models and human. Enhanced NO production is observed in various compartment in vivo but inflammatory synovium and cartilage are the major source of NO. The onset of arthritis in rodent models is successfully blocked by the NOS inhibitor, NG-monomethyl-L-arginine (L-NMMA). These data suggest a possible involvement of NO in the pathogenesis and tissue destruction in arthritis, and the significance of up-regulated NO production is discussed.