Document Detail


Effect of administration of a recombinant adenovirus expressing the genes for IFN-gamma and interleukin-12 on acute murine toxoplasmosis.
MedLine Citation:
PMID:  11710988     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effect of recombinant murine interferon-gamma (rMuIFN-gamma) produced from an adenovirus construct on Toxoplasma gondii in tissue culture and on the outcome of a T. gondii infection in mice was determined. Supernatants from AdCMVMuIFN-gamma-infected mouse lung epithelial (MuLE) cells were evaluated for the ability to produce biologically active IFN-gamma by measuring the capacity of the supernatants to activate peritoneal macrophages for killing of T. gondii. The bioactivity of IFN-gamma in supernatants increased with increasing multiplicity of infection (moi). Replication was inhibited 43%, 67%, and 70% by supernatants from MuLE cells infected with AdCMVMuIFN-gamma moi 5, 10, and 50, respectively, (p < 0.01 compared with controls). Bioactivity of IFN-gamma also increased as the length of time after infection increased. T. gondii replication was inhibited 28% and 36%, respectively, by AdCMVMuIFN-gamma-infected MuLE cell supernatants recovered at 24 and 48 h (p < 0.01 compared with control). In vivo administration of AdCMVMuIFN-gamma exhibited 33% mortality by day 9 in mice acutely infected with T. gondii compared with 100% mortality in control mice (p = 0.045). Administration of AdCMVIL-12 reduced mortality to 40% compared with control mice. However, this reduction was not significant (p = 0.08). Overall survival was extended 2 days with AdCMVMuINF-gamma administration and 5 days with AdCMVIL-12. AdCMVMuIFN-gamma in vitro inhibits T. gondii, and in vivo AdCMVMuIFN-gamma and AdCMVIL-12 lead to increased survival in mice.
Authors:
D G Mack; H A Jaffe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research     Volume:  21     ISSN:  1079-9907     ISO Abbreviation:  J. Interferon Cytokine Res.     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-11-16     Completed Date:  2002-02-01     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9507088     Medline TA:  J Interferon Cytokine Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  777-83     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology, University of Chicago, Chicago, IL 60637, USA. dmack@midway.uchicago.edu
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Adenoviridae / genetics*
Animals
Cell Line
Cells, Cultured
Culture Media, Conditioned / pharmacology
DNA, Recombinant / administration & dosage
DNA, Viral / genetics
Female
Gene Therapy*
Interferon-gamma / genetics*,  immunology,  metabolism
Interleukin-12 / genetics*,  metabolism
Kinetics
Macrophage Activation
Macrophages, Peritoneal / drug effects,  immunology
Mice
Respiratory Mucosa / immunology,  virology
Survival Analysis
Toxoplasma / drug effects,  growth & development
Toxoplasmosis, Animal / immunology,  therapy*
Transcription, Genetic
Chemical
Reg. No./Substance:
0/Culture Media, Conditioned; 0/DNA, Recombinant; 0/DNA, Viral; 187348-17-0/Interleukin-12; 82115-62-6/Interferon-gamma

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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