The role of endogenous IFN-gamma, TNF-alpha and IL-10 in LPS-induced nitric oxide release in a mouse model.
Mice injected with lipopolysaccharide (LPS) develop lethal septic shock, accompanied by elevated serum NOx, interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha) and TNF-receptor levels. Elevated NO levels are thought to play a central role in tissue damage observed during septic shock. In vitro data indicate that IFN-gamma and TNF-alpha play an important role in LPS-induced NO release. Further, interleukin 10 (IL-10) has been shown to inhibit the release of pro-inflammatory cytokines such as IFN-gamma and TNF-alpha. Therefore, in the present study, we investigated the role of IFN-gamma, TNF-alpha, and IL-10 in LPS-induced NO release. To this end, mice were pretreated with anti-IFN-gamma, anti-TNF-alpha, anti-IL-10 mAbs or combinations of these 2 h before LPS-challenge. The results indicate that IFN-gamma, TNF-alpha as well as IL-10 are involved in the regulation of LPS-induced NO release. Blocking either IFN-gamma or TNF-alpha has no effect on LPS-induced NO release, however, blocking both IFN-gamma and TNF-alpha nearly completely prevents NO release after LPS challenge, suggesting that the presence of either TNF-alpha or IFN-gamma is essential for induction of NO release after LPS challenge. Further, the results obtained with anti-IL-10 treatment suggest the presence of an IL-10 inducible factor which together with IFN-gamma and TNF-alpha regulates LPS-induced NO release.
ter Steege
J C
JC
Department of Pediatrics, Academic Hospital Maastricht, The Netherlands.
van de Ven
M W
MW
Forget
P P
PP
Brouckaert
P
P
Buurman
W A
WA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D005260:Female; D007371:Interferon-gamma / Q000276:immunology / Q000502:physiology*; D016753:Interleukin-10 / Q000276:immunology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D008934:Mitogens; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma