Multiple roles for IL-12 in a model of acute septic peritonitis.
The present study addressed the role of IL-12 in a murine model of septic peritonitis, induced by cecal ligation and puncture (CLP). Although CLP surgery induced IL-12 production at 6 and 24 h after surgery, IL-12 immunoneutralization was clearly deleterious in this model: 54% of CLP mice receiving preimmune serum survived, whereas mice administered IL-12 antisera prior to CLP experienced a 25% survival rate. IL-12 immunoneutralization not only led to increased mortality, but also appeared to promote a shift away from IL-12 and IFN-gamma, in favor of IL-10. This cytokine shift corresponded to changes in bacterial load, as CLP mice receiving IL-12 antiserum yielded more CFUs from the peritoneal cavity at 24 h after CLP. To address the role of bacterial infection in IL-12 antiserum-induced mortality following CLP, antibiotics were administered for 4 days after surgery. Despite regular antibiotic administration, IL-12 immunoneutralization still reduced survival in CLP mice. Furthermore, histology of the ceca revealed that mice administered IL-12 antisera failed to show typical organization of the damaged cecum wall. Accordingly, Gram staining revealed bacteria within peritoneal fluids from these mice, while peritoneal fluids from CLP mice that received preimmune serum and antibiotics were free of bacteria. Altogether, these data suggested multiple important roles for IL-12 in the evolution of murine septic peritonitis.
Steinhauser
M L
ML
Department of Pathology, Division of Pulmonary and Critical Care, University of Michigan Medical School, Ann Arbor 48109, USA.
Hogaboam
C M
CM
Lukacs
N W
NW
Strieter
R M
RM
Kunkel
S L
SL
D000208:Acute Disease; D000818:Animals; D002429:Cecal Diseases / Q000276:immunology / Q000382:microbiology; D015377:Cilastatin / Q000627:therapeutic use; D000077728:Cilastatin, Imipenem Drug Combination; D004195:Disease Models, Animal; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D005260:Female; D005355:Fibrosis; D015378:Imipenem / Q000627:therapeutic use; D007106:Immune Sera / Q000008:administration & dosage; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D007416:Intestinal Perforation / Q000276:immunology / Q000382:microbiology; D008026:Ligation; D051379:Mice; D010537:Peritoneum / Q000382:microbiology; D010538:Peritonitis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D014945:Wound Healing / Q000276:immunology
D004338:Drug Combinations; D007106:Immune Sera; D016753:Interleukin-10; D015377:Cilastatin; D018664:Interleukin-12; D015378:Imipenem; D007371:Interferon-gamma; D000077728:Cilastatin, Imipenem Drug Combination