Hospital readmission due to dehydration or renal failure following ileostomy creation is common, with age >50 being the strongest predictor for renal failure. Appropriate strategies to decrease dehydration and renal failure following ileostomy creation need to be investigated.

Objectives Matrix metalloproteinase-8 (MMP-8) mRNA expression was previously found to be increased in whole blood of children with septic shock. The impact of this finding on the severity and inflammatory response to sepsis is unknown. Here, we investigate the relationship between MMP-8 and disease severity in a children with septic shock. We further corroborate the role of MMP-8 in sepsis in a murine model. Design Retrospective observational clinical study and randomized controlled laboratory experiments. Setting Pediatric intensive care units and an animal research facility at an academic children’s hospital. Patients/Subjects Patients age ≤ 10 years admitted to the intensive care unit with a diagnosis of septic shock. For laboratory studies, we utilized male mice deficient for MMP-8 and male wild type C57/Bl6 mice. Interventions Blood from children with septic shock was analyzed for MMP-8 mRNA expression and MMP-8 activity, and correlated with disease severity based on mortality and degree of organ failure. A murine model of sepsis was used to explore the effect of genetic and pharmacologic inhibition of MMP-8 on the inflammatory response to sepsis. Finally, activation of nuclear factor-κB (NF-κB) was assessed both in vitro and in vivo. Measurements and Main Results Increased MMP-8 mRNA expression and activity in septic shock correlates with decreased survival and increased organ failure in pediatric patients. Genetic and pharmacologic inhibition of MMP-8 leads to improved survival and a blunted inflammatory profile in a murine model of sepsis. We also identify MMP-8 as a direct in vitro activator of the pro-inflammatory transcription factor, NF-κB. Conclusions MMP-8 is a novel modulator of inflammation during sepsis and a potential therapeutic target.