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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1998-3-31
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pubmed:abstractText |
IL-12 plays a key role in stimulating both innate and antigen-specific immune responses against a number of intracellular pathogens. A neutralizing anti-IL-12 monoclonal antibody (mAb) was used to define and compare the role of endogenous IL-12 in the liver and spleen of mice infected with Leishmania donovani. IL-12 neutralization both early and late in infection caused delayed resolution of parasite load, a transient decrease in IFN-gamma, IL-4, TNF-alpha and inducible nitric oxide synthase (NOS-2) production, and suppressed tissue granuloma formation in the liver of genetically susceptible BALB/c mice. In contrast to the liver of BALB/c mice, neutralization of IL-12 had no effect on parasite burden in the spleen over the first 28 days of infection. However, IL-12 appeared to be critical for the development of mechanisms which subsequently contain the growth of persistent parasites in this organ in that neutralization of IL-12 dramatically enhanced parasite growth after day 28 of infection. Following IL-12 neutralization, the later unchecked growth of parasites in the spleen was coincident with an extensive breakdown of the tissue microarchitecture. Immunohistochemical studies revealed that IL-12 was largely produced by uninfected cells in L. donovani-infected BALB/c mice. In contrast, the course of infection in the liver and spleen of genetically resistant CBA/n mice was unaffected by the administration of anti-IL-12 mAb. These results suggest that the liver and spleen in susceptible BALB/c mice have different temporal requirements for IL-12 in controlling L. donovani infection, whereas IL-12 plays little role in either organ in resistant CBA/n mice. In addition, IL-12 appears to be involved in the generation of both Th1 and Th2 responses during L. donovani infection in BALB/c mice.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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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 |
669-80
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pubmed:dateRevised |
2009-9-29
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pubmed:meshHeading |
pubmed-meshheading:9521077-Animals,
pubmed-meshheading:9521077-Antibodies, Monoclonal,
pubmed-meshheading:9521077-Cricetinae,
pubmed-meshheading:9521077-Cytokines,
pubmed-meshheading:9521077-Female,
pubmed-meshheading:9521077-Host-Parasite Interactions,
pubmed-meshheading:9521077-Immunity, Innate,
pubmed-meshheading:9521077-Interleukin-12,
pubmed-meshheading:9521077-Leishmania donovani,
pubmed-meshheading:9521077-Leishmaniasis, Visceral,
pubmed-meshheading:9521077-Liver,
pubmed-meshheading:9521077-Mesocricetus,
pubmed-meshheading:9521077-Mice,
pubmed-meshheading:9521077-Mice, Inbred BALB C,
pubmed-meshheading:9521077-Mice, Inbred CBA,
pubmed-meshheading:9521077-Organ Specificity,
pubmed-meshheading:9521077-Species Specificity,
pubmed-meshheading:9521077-Spleen,
pubmed-meshheading:9521077-Th1 Cells,
pubmed-meshheading:9521077-Th2 Cells
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pubmed:year |
1998
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pubmed:articleTitle |
Neutralization of IL-12 demonstrates the existence of discrete organ-specific phases in the control of Leishmania donovani.
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pubmed:affiliation |
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, GB. c.engwerda@lshtm.ac.uk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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