Abstract
Department of Pediatrics, Academic Hospital Maastricht, The Netherlands.
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.
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.
| Original language | English |
|---|---|
| Pages (from-to) | 115-123 |
| Number of pages | 9 |
| Journal | Cytokine |
| Volume | 10 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 1 Jan 1998 |