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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
1998-8-13
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pubmed:abstractText |
In several models of inflammation, including collagen-induced arthritis (CIA), the disease-promoting effect of IL-12 has been attributed to its well-known ability to produce IFN-gamma. However, IFN-gamma receptor knockout (IFN-gammaR KO) mice of the DBA/1 strain have been reported to be more susceptible to CIA than corresponding wild-type mice, indicating the existence of an IFN-gamma-mediated protective pathway in this model. In the present study the development of CIA was found to be completely prevented by pretreatment with a neutralizing anti-IL-12 antibody, not only in wild-type, but significantly also in IFN-gammaR KO mice. In both strains of mice, the protective effect of anti-IL-12 was associated with lower production of anti-collagen type II antibodies. In vivo stimulation with anti-CD3 antibody in arthritic IFN-gammaR KO mice resulted in production of higher levels of circulating IFN-gamma, TNF and IL-2 than in corresponding control mice that had not received the arthritis-inducing immunization. This was not the case in arthritis-developing wild-type mice. Furthermore, the protective effect of anti-IL-12 antibody in mutant, but not in wild-type mice, was associated with lower circulating IFN-gamma, TNF and IL-2 and higher IL-4 and IL-5 cytokine levels following an anti-CD3 challenge. The data indicate that IL-12 promotes the development of arthritis independently of its ability to induce or favor production of IFN-gamma. In fact, any IFN-gamma produced in the course of the disease process rather exerts a protective effect. Furthermore, our study suggests that, in the absence of a functional IFN-gamma system, endogenous IL-12 exerts its disease-promoting effect by favoring production of other Th1-associated cytokines (IL-2 and TNF), by inhibiting development of IL-4- and IL-5-producing T cells and by stimulating production of anti-collagen autoantibodies.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interferon,
http://linkedlifedata.com/resource/pubmed/chemical/interferon gamma receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0014-2980
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
28
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2143-51
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9692883-Animals,
pubmed-meshheading:9692883-Arthritis,
pubmed-meshheading:9692883-Collagen,
pubmed-meshheading:9692883-Cytokines,
pubmed-meshheading:9692883-Immunoglobulin G,
pubmed-meshheading:9692883-Interferon-gamma,
pubmed-meshheading:9692883-Interleukin-12,
pubmed-meshheading:9692883-Mice,
pubmed-meshheading:9692883-Mice, Inbred DBA,
pubmed-meshheading:9692883-Mice, Knockout,
pubmed-meshheading:9692883-Receptors, Interferon
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pubmed:year |
1998
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pubmed:articleTitle |
Anti-IL-12 antibody prevents the development and progression of collagen-induced arthritis in IFN-gamma receptor-deficient mice.
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pubmed:affiliation |
Immunobiology, Rega Institute, University of Leuven, Belgium. patrick.matthys@rega.kuleuven.ac.be
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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