Neutralization of IL-18 reduces neutrophil tissue accumulation and protects mice against lethal Escherichia coli and Salmonella typhimurium endotoxemia
- PMID: 10679104
- DOI: 10.4049/jimmunol.164.5.2644
"VSports手机版" Neutralization of IL-18 reduces neutrophil tissue accumulation and protects mice against lethal Escherichia coli and Salmonella typhimurium endotoxemia
Abstract (VSports注册入口)
In addition to stimulating IFN-gamma synthesis, IL-18 also possesses inflammatory effects by inducing synthesis of the proinflammatory cytokines TNF and IL-1beta and the chemokines IL-8 and macrophage inflammatory protein-1alpha. We hypothesized that neutralization of IL-18 would have a beneficial effect in lethal endotoxemia in mice. IL-1beta converting enzyme (ICE)-deficient mice, lacking the ability to process mature IL-18 and IL-1beta, were completely resistant to lethal endotoxemia induced by LPS derived from either Escherichia coli or Salmonella typhimurium. In contrast, both wild-type and IL-1beta-/- mice were equally susceptible to the lethal effects of LPS, implicating that absence of mature IL-18 or IFN-gamma but not IL-1beta in ICE-/- mice is responsible for this resistance. However, IFN-gamma-deficient mice were not resistant to S. typhimurium LPS, suggesting an IFN-gamma-independent role for IL-18. Anti-IL-18 Abs protected mice against a lethal injection of either LPS. Anti-IL-18 treatment also reduced neutrophil accumulation in liver and lungs. The increased survival was accompanied by decreased levels of IFN-gamma and macrophage inflammatory protein-2 in anti-IL-18-treated animals challenged with E VSports手机版. coli LPS, whereas IFN-gamma and TNF concentrations were decreased in treated mice challenged with S. typhimurium. In conclusion, neutralization of IL-18 during lethal endotoxemia protects mice against lethal effects of LPS. This protection is partly mediated through inhibition of IFN-gamma production, but mechanisms involving decreased neutrophil-mediated tissue damage due to the reduction of either chemokines (E. coli LPS) or TNF (S. typhimurium LPS) synthesis by anti-IL-18 treatment may also be involved. .
Publication types
- Actions (VSports)
"VSports在线直播" MeSH terms
- Actions (V体育2025版)
- "V体育ios版" Actions
- "VSports注册入口" Actions
- Actions (VSports手机版)
- Actions (VSports)
- Actions (VSports)
- Actions (VSports app下载)
- "VSports最新版本" Actions
- Actions (V体育2025版)
- "V体育2025版" Actions
- "V体育2025版" Actions
- V体育安卓版 - Actions
- Actions (VSports最新版本)
- V体育2025版 - Actions
- "V体育安卓版" Actions
"VSports注册入口" Substances
- V体育安卓版 - Actions
- VSports手机版 - Actions
- Actions (VSports手机版)
- VSports app下载 - Actions
Grants and funding
"VSports" LinkOut - more resources
Full Text Sources
"V体育2025版" Other Literature Sources
Medical
Molecular Biology Databases (V体育2025版)
Miscellaneous