Suppression of arthritis by an inhibitor of nitric oxide synthase.
Nitric oxide (NO), a toxic radical gas produced during the metabolism of L-arginine by NO synthase (NOS), has been implicated as a mediator of immune and inflammatory responses. A single injection of streptococcal cell wall fragments (SCW) induces the accumulation of inflammatory cells within the synovial tissue and a cell-mediated immune response that leads destructive lesions. We show here that NO production is elevated in the inflamed joints of SCW-treated rats. Administration of NG-monomethyl-L-arginine, an inhibitor of NOS, profoundly reduced the synovial inflammation and tissue damage as measured by an articular index and reflected in the histopathology. These studies implicate the NO pathway in the pathogenesis of an inflammatory arthritis and demonstrate the ability of a NOS inhibitor to modulate the disease.
McCartney-Francis
N
N
Laboratory of Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Allen
J B
JB
Mizel
D E
DE
Albina
J E
JE
Xie
Q W
QW
Nathan
C F
CF
Wahl
S M
SM
D000208:Acute Disease; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy* / Q000209:etiology; D002473:Cell Wall; D046508:Culture Techniques; D005260:Female; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase; D051381:Rats; D017207:Rats, Sprague-Dawley; D013291:Streptococcus; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases