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

Objective To assess the impact of different doses of anti-interferon gamma (anti-IFN gamma) 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-IFN gamma 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)-1 beta, IL-6, IL-10 and IFN gamma 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-1 beta and IL-10 concentrations. As therapy, anti-IFN gamma fragments were protective only when initiated 24 h after CLP. Conclusions Delicate modulation of IFN gamma at the correct timing, even when the septic process has begun, is an exciting alternative to explore in the treatment of sepsis.