Document Detail


Enhanced survival from CLP-induced sepsis following late administration of low doses of anti-IFNγ F(ab')2 antibody fragments.
MedLine Citation:
PMID:  21725677     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To assess the impact of different doses of anti-interferon gamma (anti-IFNγ) F(ab')2 fragments, administered prophylactically, on survival and on serum concentration of cytokines in a murine model of sepsis induced by cecal ligation and puncture (CLP). We further explore the impact of therapeutic administration of the most protective dose on survival.
SUBJECTS AND TREATMENT: Balb/c mice were prophylactically treated by the intraperitoneal route with anti-IFNγ initiated 2 h before CLP and every 24 h for a total of five times in each of the following doses: 0.01, 0.1, or 1 mg/kg. Sham and control groups received sterile saline solution in a similar scheme.
METHODS: Serum tumor necrosis factor (TNF), interleukin (IL)-1β, IL-6, IL-10 and IFNγ were measured at 3, 24 and 48 h after CLP by ELISA. Survival curves were compared using a Mantel-Haenzel method.
RESULTS: Significant prophylactic protection was found only with 0.01 mg/kg, in association with regulation of IL-1β and IL-10 concentrations. As therapy, anti-IFNγ fragments were protective only when initiated 24 h after CLP.
CONCLUSIONS: Delicate modulation of IFNγ at the correct timing, even when the septic process has begun, is an exciting alternative to explore in the treatment of sepsis.
Authors:
R Márquez-Velasco; A X Martínez-Velázquez; L M Amezcua-Guerra; F Flores-Guzmán; A Díaz-Quiñonez; F Massó; J Paniagua-Solís; R Bojalil
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-07-02
Journal Detail:
Title:  Inflammation research : official journal of the European Histamine Research Society ... [et al.]     Volume:  60     ISSN:  1420-908X     ISO Abbreviation:  Inflamm. Res.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-13     Completed Date:  2012-01-05     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  9508160     Medline TA:  Inflamm Res     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  947-53     Citation Subset:  IM    
Affiliation:
Departament of Immunology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano #1, Tlalpan, 14080 Mexico City, Mexico.
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay / methods
Humans
Immunoglobulin Fragments / chemistry*
Interferon-gamma / biosynthesis,  metabolism*
Interleukin-10 / biosynthesis
Interleukin-1beta / biosynthesis
Interleukin-6 / biosynthesis
Male
Mice
Mice, Inbred BALB C
Recombinant Proteins / metabolism
Sepsis / immunology*,  pathology
Time Factors
Chemical
Reg. No./Substance:
0/Immunoglobulin Fragments; 0/Interleukin-1beta; 0/Interleukin-6; 0/Recombinant Proteins; 130068-27-8/Interleukin-10; 82115-62-6/Interferon-gamma

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