NEC is sometimes dubbed the specter of neonatal intensive care units (NICUs), as its onset is insidiously non-specific, but once NEC becomes manifest, it often wreaks disastrous intestinal and systemic havoc. Short- and long-term consequences are grave, including up to 60% mortality and severe neurodevelopmental impairment in 25% of the survivors. The understanding of NEC pathophysiology is poor; thus, no specific therapy exists. We hypothesize that an inappropriate inflammatory response towards bacterial colonisation and/or food components plays a pivotal role in the initiation and perpetuation of NEC. Hence, we set out to explore anti-inflammatory strategies in a murine model of this disease.
NEC was induced in newborn mice using a combination of some of the risk factors known to precipitate human NEC, including formula feeding, hypoxia and cold stress, in mice transgenic for IL-37 (a powerful anti-inflammatory cytokine we recently described), and in wild-type (WT) controls.
Whereas WT mice exhibited clinical and histological features of NEC, IL-37 transgenic (tg) mice were largely protected from intestinal injury. On a 0-3 scale (no to severe pathology), scores were 1.3 (WT) vs 0.6 (IL-37tg) for ileus, 1.3 vs 0.3 for hematochezia and 1 vs 0 for diarrhea. This protective effect of IL-37 was also evident histologically: tissue injury scores assessing epithelial vacuolation and mucosal disintegration were 3 (WT) vs 1 (IL-37tg) in the duodenum, 2.2 vs 0.5 in the jejunum and 2.3 vs 1 in the ileum. This marked amelioration of NEC severity in IL-37tg mice was accompanied by a reduction in IL-1βeta mRNA.
In summary, early results from this study show that IL-37 protects newborn mice against NEC, indicating that excessive inflammation contributes to disease progression. Blocking the inappropriate inflammatory response of NEC may represent a promising approach to improve the outlook of babies suffering from this devastating disease.