These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Susceptibility to Pneumocystis carinii in mice is dependent on simultaneous deletion of IFN-gamma and type 1 and 2 TNF receptor genes.
    Author: Rudmann DG, Preston AM, Moore MW, Beck JM.
    Journal: J Immunol; 1998 Jul 01; 161(1):360-6. PubMed ID: 9647244.
    Abstract:
    Pneumocystis carinii pneumonia is an important cause of morbidity and mortality in immunosuppressed patients, particularly HIV-infected individuals. An improved understanding of pulmonary host response, including the cytokines required for defense, could suggest novel immunotherapeutic approaches to this infection. The cytokines IFN-gamma and TNF have contributory roles in host defense against P. carinii, but their combined and interactive importance is unclear. To test the roles of these cytokines in defense against P. carinii directly, organisms were inoculated intratracheally into wild-type mice and into three groups of gene-deleted mice: those lacking genes for IFN-gamma (IFN-gamma(-/-)), for TNF receptors 1 and 2 (TNFR(-/-)), and for both IFN-gamma and TNFR (TNFR-IFN-gamma(-/-)). Four weeks after P. carinii inoculation, lungs of the wild-type, IFN-gamma(-/-), and TNFR(-/-) mice demonstrated clearance of P. carinii and only mild inflammation. However, TNFR-IFN-gamma(-/-) mice demonstrated severe P. carinii infection and lung inflammation. Our findings demonstrate conclusively that deletion of either IFN-gamma or TNF activity alone does not block clearance of P. carinii. However, simultaneous deletion of IFN-gamma and TNF receptor genes results in susceptibility to P. carinii. Rather than focusing exclusively on individual cytokines, our data suggest that immunotherapy targeted at maximizing both the IFN-gamma and TNF responses to P. carinii may be required to augment host defense against this important opportunistic pathogen.
    [Abstract] [Full Text] [Related] [New Search]