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*
Department of Immunology, University of Glasgow, Glasgow, United Kingdom; and
Department of Bacteriology, Glasgow Royal Infirmary, Glasgow, United Kingdom
Nitric oxide (NO), produced in large amounts by inducible NO
synthase (iNOS), has emerged recently as an important microbicidal and
immunomodulatory mediator. We have investigated its role in bacterial
septic arthritis caused by Staphylococcus aureus infection
using iNOS-deficient mice. The incidence, rate of development, and
severity of arthritis were greater in iNOS-deficient than in
heterozygous or wild-type control mice. Similarly, the incidence and
severity of septicemia and mortality were significantly higher in
iNOS-deficient mice compared with controls. Increased TNF-
synthesis
in vivo and in vitro and enhanced IFN-
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 for severe articular destruction and
imply that NO is of importance in synovial defense against
staphylococcal infection.
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