Linked Life Data

10679104

Source:http://linkedlifedata.com/resource/pubmed/id/10679104

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2000-3-23
pubmed:abstractText
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. 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
164
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2644-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10679104-Animals, pubmed-meshheading:10679104-Cell Movement, pubmed-meshheading:10679104-Chemokines, pubmed-meshheading:10679104-Endotoxemia, pubmed-meshheading:10679104-Escherichia coli Infections, pubmed-meshheading:10679104-Immune Sera, pubmed-meshheading:10679104-Injections, Intraperitoneal, pubmed-meshheading:10679104-Interferon-gamma, pubmed-meshheading:10679104-Interleukin-18, pubmed-meshheading:10679104-Lipopolysaccharides, pubmed-meshheading:10679104-Liver, pubmed-meshheading:10679104-Lung, pubmed-meshheading:10679104-Mice, pubmed-meshheading:10679104-Mice, Inbred C57BL, pubmed-meshheading:10679104-Mice, Knockout, pubmed-meshheading:10679104-Neutrophils, pubmed-meshheading:10679104-Peroxidase, pubmed-meshheading:10679104-Salmonella Infections, Animal, pubmed-meshheading:10679104-Salmonella typhimurium, pubmed-meshheading:10679104-Tumor Necrosis Factor-alpha
pubmed:year
2000
pubmed:articleTitle
Neutralization of IL-18 reduces neutrophil tissue accumulation and protects mice against lethal Escherichia coli and Salmonella typhimurium endotoxemia.
pubmed:affiliation
Departments ofMedicine and Surgery, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't