Increased Inflammatory Reaction to Intestinal Ischemia-Reperfusion in Neonatal versus Adult Mice

Abstract

Aim Neonate and preterm patients are threatened by exaggerated inflammation of the gut. This study tests the hypothesis that the neonatal gut is prone to inflammation, by comparing the inflammatory reaction of neonatal and adult murine intestine to ischemia and reperfusion.

Methods Neonatal (4 days, n = 36) and adult (4 weeks, n = 12) C57BL/6J mice were randomly divided between ischemia-reperfusion (IR) and untreated controls (Con). In IR animal's intestinal ischemia was induced by clamping the superior mesenteric artery (30 minutes) followed by reperfusion (4 hours). After the experiment, RNA was extracted from the small intestines and the expression of the chemokines CXCL1/KC and CXCL2/MIP-2 were determined by quantitative real-time reverse transcription-polymerase chain reaction. Flow cytometry was used to analyze neutrophil influx (Live+ Ly-6G + ) in isolated cell populations.

Results We observed a strong increase in all measured proinflammatory endpoints after IR in both adult and neonatal mice. However, the inflammatory reaction was significantly stronger in neonatal murine intestines, with a significantly higher increase in CXCL1/KC expression and neutrophil accumulation as compared with adults (p < 0.05).

Conclusion The intestines of neonatal mice reacted with an increased inflammatory response to the ischemic insult. This increased susceptibility could help to explain the exaggerated inflammation seen in diseases such as necrotizing enterocolitis.

Keywords

gut - neutrophils - CXCL1 - CXCL2 - age

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