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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2003-7-8
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pubmed:abstractText |
IL-18 expression and functional activity have been associated with a range of autoimmune diseases. However, the precise mechanism by which IL-18 induces such pathology remains unclear. In this study we provide direct evidence that IL-18 activates neutrophils via TNF-alpha induction, which drives the production of leukotriene B(4) (LTB(4)), which in turn leads to neutrophil accumulation and subsequent local inflammation. rIL-18 administered i.p. resulted in the local synthesis of LTB(4) and a rapid influx of neutrophils into the peritoneal cavity, which could be effectively blocked by the LTB(4) synthesis inhibitor MK-886 (MK) or its receptor antagonist CP-105,696. IL-18-induced neutrophils recruitment and LTB(4) production could also be blocked by a neutralizing anti-TNF-alpha Ab. In addition, IL-18 failed to induce neutrophil accumulation in vivo in TNFRp55(-/-) mice. In an IL-18-dependent murine collagen-induced arthritis model, administration of MK significantly inhibited disease severity and reduced articular inflammation and joint destruction. Furthermore, MK-886-treated mice also displayed suppressed proinflammatory cytokine production in response to type II collagen in vitro. Finally, we showed that IL-18-activated human peripheral blood neutrophils produced significant amounts of LTB(4) that were effectively blocked by the MK. Together, these findings provide a novel mechanism whereby IL-18 can promote inflammatory diseases.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
171
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1009-15
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12847274-Adjuvants, Immunologic,
pubmed-meshheading:12847274-Administration, Oral,
pubmed-meshheading:12847274-Animals,
pubmed-meshheading:12847274-Arthritis, Experimental,
pubmed-meshheading:12847274-Arthritis, Rheumatoid,
pubmed-meshheading:12847274-Cells, Cultured,
pubmed-meshheading:12847274-Chemotaxis, Leukocyte,
pubmed-meshheading:12847274-Collagen Type II,
pubmed-meshheading:12847274-Humans,
pubmed-meshheading:12847274-Indoles,
pubmed-meshheading:12847274-Inflammation Mediators,
pubmed-meshheading:12847274-Injections, Intradermal,
pubmed-meshheading:12847274-Injections, Intraperitoneal,
pubmed-meshheading:12847274-Interleukin-18,
pubmed-meshheading:12847274-Leukotriene B4,
pubmed-meshheading:12847274-Male,
pubmed-meshheading:12847274-Mice,
pubmed-meshheading:12847274-Mice, Inbred BALB C,
pubmed-meshheading:12847274-Mice, Inbred C57BL,
pubmed-meshheading:12847274-Mice, Inbred DBA,
pubmed-meshheading:12847274-Mice, Knockout,
pubmed-meshheading:12847274-Neutrophil Infiltration,
pubmed-meshheading:12847274-Neutrophils,
pubmed-meshheading:12847274-Severity of Illness Index,
pubmed-meshheading:12847274-Tumor Necrosis Factor-alpha
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pubmed:year |
2003
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pubmed:articleTitle |
IL-18 enhances collagen-induced arthritis by recruiting neutrophils via TNF-alpha and leukotriene B4.
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pubmed:affiliation |
Department of Pharmacology, School of Medicine Ribeirao Preto, University of São Paulo, São Paulo, Brazil.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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