Interferon-gamma increases mortality following cecal ligation and puncture.
Interferon-gamma (IFN-gamma) has been demonstrated to improve outcome following localized infection and hemorrhagic shock in experimental studies. We sought to determine the effects of IFN-gamma in a clinically relevant murine model of intra-abdominal polymicrobial sepsis. Fifty male BDF1 mice, each weighing 23-28 g, underwent cecal ligation and puncture (CLP) followed by administration of subcutaneous injections of IFN-gamma 100-22,500 U or vehicle control immediately post-CLP and then daily. In a second set of experiments, 60 mice underwent daily injections of vehicle control or 100 U IFN-gamma 24, 48, or 72 hours prior to CLP. Interferon-gamma administered following CLP led to increased mortality and earlier deaths in a dose-dependent fashion (p < 0.05). Interferon-gamma given 24, 48, or 72 hours prior to CLP resulted in no demonstrable benefit when compared with animals that did not receive IFN-gamma (p = 0.14, p = 0.94, and p = 0.97, respectively). While IFN-gamma has been reported to be of value in selected clinical situations by improving resistance to infection, it may not be capable of conferring protection following surgery or trauma with intra-abdominal sepsis, and in fact may be detrimental.
Miles
R H
RH
Department of Surgery, Loyola University Medical Center, Maywood, Illinois 60153.
Paxton
T P
TP
Dries
D J
DJ
Gamelli
R L
RL
D000818:Animals; D002432:Cecum / Q000601:surgery*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008026:Ligation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011292:Premedication; D011677:Punctures; D011994:Recombinant Proteins; D013530:Surgical Wound Infection / Q000401:mortality / Q000517:prevention & control*; D015996:Survival Rate
D011994:Recombinant Proteins; D007371:Interferon-gamma