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Enhanced survival from CLP-induced sepsis following late administration of low doses of anti-IFNγ F(ab′)2 antibody fragments

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Abstract

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.

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Acknowledgments

This study was supported by Laboratorios Silanes, S. A. de C. V and FUNSALUD, Mexico.

Author information

Authors and Affiliations

  1. Departament of Immunology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano #1, Tlalpan, 14080, Mexico City, Mexico

    R. Márquez-Velasco, A. X. Martínez-Velázquez, L. M. Amezcua-Guerra & R. Bojalil

  2. Laboratorios Silanes, S. A. de C. V., Amores 1304, 03100, Col del Valle, Mexico City, Mexico

    J. Paniagua-Solís

  3. División de Laboratorios de Vigilancia e Investigación Epidemiológica, CMN La Raza, Instituto Mexicano del Seguro Social, Mexico City, Mexico

    A. Díaz-Quiñonez

  4. Department of Physiology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico

    F. Massó

  5. Department of Health Care, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico

    R. Bojalil

  6. Department of Health Sciences, Universidad del Valle de México, Mexico City, Mexico

    R. Márquez-Velasco

  7. Cancer Unit, German Cancer Research Center, Heidelberg, Germany

    F. Flores-Guzmán

Authors
  1. R. Márquez-Velasco
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  2. A. X. Martínez-Velázquez
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  3. L. M. Amezcua-Guerra
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  4. F. Flores-Guzmán
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  5. A. Díaz-Quiñonez
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  6. F. Massó
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  7. J. Paniagua-Solís
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  8. R. Bojalil
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Corresponding author

Correspondence to R. Bojalil.

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Responsible Editor: Artur Bauhofer.

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Márquez-Velasco, R., Martínez-Velázquez, A.X., Amezcua-Guerra, L.M. et al. Enhanced survival from CLP-induced sepsis following late administration of low doses of anti-IFNγ F(ab′)2 antibody fragments. Inflamm. Res. 60, 947–953 (2011). https://doi.org/10.1007/s00011-011-0355-0

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  • DOI: https://doi.org/10.1007/s00011-011-0355-0

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