Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-3-31
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
669-80
pubmed:dateRevised
2009-9-29
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
pubmed:year
1998
pubmed:articleTitle
Neutralization of IL-12 demonstrates the existence of discrete organ-specific phases in the control of Leishmania donovani.
pubmed:affiliation
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, GB. c.engwerda@lshtm.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't