SEPTIC ARTHRITIS FOLLOWING STAPHYLOCOCCUS-AUREUS INFECTION IN MICE LACKING INDUCIBLE NITRIC-OXIDE SYNTHASE

Nitric oxide (NO), produced in large amounts by inducible NO synthase (iNOS), has emerged recently as an important microbicidal and immunomo dulatory mediator. We have investigated its role in bacterial septic a rthritis caused by Staphylococcus aureus infection using iNOS-deficien t mice. The incidence, rate of development, and severity of arthritis were greater in iNOS-deficient than in heterozygous or wild-type contr ol mice. Similarly, the incidence and severity of septicemia and morta lity were significantly higher in iNOS-deficient mice compared with co ntrols. Increased TNF-alpha synthesis in vivo and in vitro and enhance d IFN-gamma compared with IL-4 production in vitro in iNOS-mutant mice demonstrated exaggerated Th1 polarization of the host response. These data indicate that high output NO production is not a prerequisite fo r severe articular destruction and imply that NO is of importance in s ynovial defense against staphylococcal infection.