Perioperative anti-α4β7 Integrin Blockade Alters Wound Cell Infiltrate but Not the Functional Outcome of Ileocecal Anastomoses in Mice With Crohn's-like Ileitis.

BACKGROUND AND AIMS: Crohn's disease (CD) itself is discussed as risk factors for anastomotic leakage (AL) after ileocecal resection (ICR). In order to gain insight into the mechanisms of anastomotic healing (AH) in Crohn's ileitis, we performed ICR in a mouse model of spontaneous ileitis. Additionally, we investigated the impact of anti-α4β7 integrin antibody on AH. METHODS: SAMP1/YitFc (SAMP1) and parental control (AKR) mice were subjected to ICR. Mice received an anti-α4β7 integrin antibody or isotype control (25 mg/kg). Functional (bursting pressure), macroscopic (healing score), and matrix-related parameters (hydroxyproline, collagenase activity, and histology) of AH were assessed at day 5. Local and systemic cytokine messenger RNA expression and lipocalin-2 in plasma and stool were measured. Effects of α4β7 integrin blockade on anastomotic cell infiltration were assessed by flow cytometry. RESULTS: SAMP1 mice exhibited a 5-fold higher rate of microabscess formation in the anastomoses and worse macroscopical healing. Functional healing and matrix parameters, as well as leak rate, were similar to AKR control mice. Despite an increase in systemic inflammation, a significant drop in T helper 1 cytokine expression was observed in the mesenteric lymph nodes of SAMP1 mice. Flow cytometric analyses revealed a higher proportion of mesenchymal cells and myeloid suppressor cells. Wound macrophages remained unchanged in the anastomotic tissue of anti-α4β7 integrin antibody-treated SAMP1 mice. CONCLUSIONS: Crohn's-like ileitis mice were at higher risk for abscess formation. Anti-α4β7 integrin treatment resulted in cellular changes that did not impair functional anastomotic healing.