RGD Reference Report - Immunomodulatory role of endogenous interleukin-18 in gamma interferon-mediated resolution of replicative Legionella pneumophila lung infection. - Rat Genome Database

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Immunomodulatory role of endogenous interleukin-18 in gamma interferon-mediated resolution of replicative Legionella pneumophila lung infection.

Authors: Brieland, JK  Jackson, C  Hurst, S  Loebenberg, D  Muchamuel, T  Debets, R  Kastelein, R  Churakova, T  Abrams, J  Hare, R  O'Garra, A 
Citation: Brieland JK, etal., Infect Immun. 2000 Dec;68(12):6567-73.
RGD ID: 4889865
Pubmed: PMID:11083766   (View Abstract at PubMed)
PMCID: PMC97751   (View Article at PubMed Central)

The in vivo role of endogenous interleukin-18 (IL-18) in modulating gamma interferon (IFN-gamma)-mediated resolution of replicative Legionella pneumophila lung infection was assessed using a murine model of Legionnaires' disease. Intratracheal inoculation of A/J mice with virulent bacteria (10(6) L. pneumophila organisms per mouse) resulted in induction of IL-18 protein in bronchoalveolar lavage fluid (BALF) and intrapulmonary expression of IL-18 mRNA. Real-time quantitative RT-PCR analysis of infected lung tissue demonstrated that induction of IL-18 in BALF preceded induction of IL-12 and IFN-gamma mRNAs in the lung. Blocking intrapulmonary IL-18 activity by administration of a monoclonal antibody (MAb) to the IL-18 receptor (anti-IL-18R MAb) prior to L. pneumophila infection inhibited induction of intrapulmonary IFN-gamma production but did not significantly alter resolution of replicative L. pneumophila lung infection. In contrast, blocking endogenous IL-12 activity by administration of anti-IL-12 MAb) alone or in combination with anti-IL-18R MAb inhibited induction of intrapulmonary IFN-gamma and resulted in enhanced intrapulmonary growth of the bacteria within 5 days postinfection. Taken together, these results demonstrate that IL-18 plays a key role in modulating induction of IFN-gamma in the lung in response to L. pneumophila and that together with IL-12, IL-18 regulates intrapulmonary growth of the bacteria.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL18HumanLegionnaires' disease  ISOIl18 (Mus musculus) RGD 
Il18RatLegionnaires' disease  ISOIl18 (Mus musculus) RGD 
Il18MouseLegionnaires' disease  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il18  (interleukin 18)

Genes (Mus musculus)
Il18  (interleukin 18)

Genes (Homo sapiens)
IL18  (interleukin 18)


Additional Information