| Abstrakt: |
Mice injected with lipopolysaccharide (LPS) develop lethal septic shock, accompanied by elevated serum NOx, interferon γ (IFN-γ), tumour necrosis factor α (TNF-α) 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-γ and TNF-α 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-γ and TNF-α. Therefore, in the present study, we investigated the role of IFN-γ, TNF-α, and IL-10 in LPS-induced NO release. To this end, mice were pretreated with anti-IFN-γ, anti-TNF-α, anti-IL-10 mAbs or combinations of these 2 h before LPS-challenge. The results indicate that IFN-γ, TNF-α as well as IL-10 are involved in the regulation of LPS-induced NO release. Blocking either IFN-γ or TNF-α has no effect on LPS-induced NO release, however, blocking both IFN-γ and TNF-α nearly completely prevents NO release after LPS challenge, suggesting that the presence of either TNF-α or IFN-γ 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-γ and TNF-α regulates LPS-induced NO release. |
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