Interferon-gamma increases mortality following cecal ligation and puncture

Area of Science:

• Immunology
• Sepsis Research
• Preclinical Models

Background:

• Interferon-gamma (IFN-gamma) has shown promise in improving outcomes for localized infections and hemorrhagic shock in experimental settings.
• Its efficacy in more complex conditions like intra-abdominal sepsis remains to be fully elucidated.

Purpose of the Study:

• To investigate the effects of IFN-gamma administration on mortality and outcomes in a murine model of polymicrobial intra-abdominal sepsis.
• To evaluate both post-sepsis induction and pre-sepsis induction administration of IFN-gamma.

Main Methods:

• A cecal ligation and puncture (CLP) model was used in male BDF1 mice.
• IFN-gamma (100-22,500 U) or vehicle control was administered subcutaneously immediately post-CLP and daily thereafter.
• In separate experiments, mice received daily injections of 100 U IFN-gamma or vehicle 24, 48, or 72 hours prior to CLP.

Main Results:

• Post-CLP administration of IFN-gamma resulted in a dose-dependent increase in mortality and earlier deaths (p < 0.05).
• Pre-treatment with IFN-gamma 24, 48, or 72 hours before CLP showed no significant survival benefit compared to controls (p = 0.14, p = 0.94, p = 0.97, respectively).

Conclusions:

• IFN-gamma administered after the onset of intra-abdominal sepsis in mice is detrimental and increases mortality.
• Pre-treatment with IFN-gamma does not confer protection in this sepsis model and may be harmful.
• These findings suggest that IFN-gamma may not be beneficial and could be detrimental in managing intra-abdominal sepsis following surgery or trauma.