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 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-alpha synthesis in vivo and in vitro and enhanced 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 for severe articular destruction and imply that NO is of importance in synovial defense against staphylococcal infection.
McInnes
I B
IB
Department of Immunology, University of Glasgow, United Kingdom.
Leung
B
B
Wei
X Q
XQ
Gemmell
C C
CC
Liew
F Y
FY
D000818:Animals; D001170:Arthritis, Infectious / Q000201:enzymology*; D001427:Bacterial Toxins; D004768:Enterotoxins / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D018805:Sepsis / Q000201:enzymology; D013154:Spleen / Q000276:immunology; D013203:Staphylococcal Infections / Q000150:complications*; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology
D001427:Bacterial Toxins; D004768:Enterotoxins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D015847:Interleukin-4; D009569:Nitric Oxide; C026066:enterotoxin A, Staphylococcal; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse