Persistent Post-Recovery Hyperinflammation of Necrotizing Enterocolitis Is Ameliorated by 5-ASA Treatment

<b><i>Background:</i></b> Necrotizing enterocolitis (NEC) is the leading gastrointestinal cause of death of premature neonates. We have previously shown that this hyperinflammatory state persists even post-recovery. We hypothesize that recovered patients with NEC will have a decreased hyperinflammatory response when the anti-inflammatory medication mesalamine (5-ASA) is administered even when exposed to in vitro NEC induction. <b><i>Methods:</i></b> Enteroids were generated and subjected to in vitro NEC induction. One half were subjected to 5-ASA treatment. Tumor necrosis factor-alpha (TNF-α) and interleukin 8 (IL-8) were evaluated via RT-qPCR. Mice underwent in vivo NEC induction, one group was given 5-ASA 50 mg/kg 12 h before the start of NEC induction. The intestine was harvested and assessed for hyperinflammatory markers and histological grading was performed. <b><i>Results:</i></b> Recovered NEC enteroids treated with 5-ASA during NEC induction show a significant decrease in inflammatory markers compared with control (p = 0.0014 TNF-α, downtrend IL-8). Active NEC enteroids treated with 5-ASA during in vitro NEC induction show a significant decrease in TNF-α RT-qPCR (p = 0.0443) and IL-8 RT-qPCR (p = 0.0265). In mice that received 5-ASA 50 mg/kg before in vivo NEC induction, there is a significant decrease in both TNF-α (p = 0.0114) and IL-8 (p = 0.0051). <b><i>Conclusion:</i></b> Enteroids and mice exposed to 5-ASA have a significant decrease in inflammatory markers. This decrease despite NEC induction in both enteroids and mice may demonstrate the impact that anti-inflammatory agents could have on treatment for NEC. This could be important given the robust hyperinflammatory response to a second hit after recovery and may impact the trajectory of an illness post-recovery from NEC.