title: Enhanced survival from CLP-induced sepsis following late administration of low doses of anti-IFNγ F(ab')2 antibody fragments.
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.
  
  
  METHODS
  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: Departament of Immunology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano #1, Tlalpan, 14080 Mexico City, Mexico.
authors: R
authors: R
authors: Márquez-Velasco
authors: A X
authors: AX
authors: Martínez-Velázquez
authors: L M
authors: LM
authors: Amezcua-Guerra
authors: F
authors: F
authors: Flores-Guzmán
authors: A
authors: A
authors: Díaz-Quiñonez
authors: F
authors: F
authors: Massó
authors: J
authors: J
authors: Paniagua-Solís
authors: R
authors: R
authors: Bojalil
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007128:Immunoglobulin Fragments / Q000737:chemistry*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000378:metabolism; D018805:Sepsis / Q000276:immunology* / Q000473:pathology; D013997:Time Factors
chemical_list: D007128:Immunoglobulin Fragments; D053583:Interleukin-1beta; D015850:Interleukin-6; D011994:Recombinant Proteins; D016753:Interleukin-10; D007371:Interferon-gamma