Fuzapladib reduces postsurgical inflammation in the intestinal muscularis externa

Abstract

Postoperative ileus (POI) is a surgical complication that induces emesis and anorexia. Fuzapladib (FUZ), an inhibitor of leukocyte-function-associated antigen type 1 (LFA-1) activation, a leukocyte adhesion molecule, exerts anti-inflammatory effects by inhibiting leukocyte migration into the inflammatory site. In this study, we examined the prophylactic impact of FUZ on POI in a mouse model. POI model mice were generated by intestinal manipulation, and the effect of FUZ on intestinal transit and the infiltration of inflammatory cells into the ileal muscularis externa was assessed. The increased number of macrophages was significantly suppressed by FUZ, whereas the infiltration of neutrophils into the ileal muscularis externa was not sufficiently inhibited in the POI model mice. Additionally, FUZ did not ameliorate delayed gastrointestinal transit in POI model mice. In conclusion, our results suggest that FUZ does not improve delayed gastrointestinal transit but partially inhibits inflammation in the ileal muscularis externa in POI model mice. FUZ may be a potential anti-inflammatory agent for the management of post-surgical inflammation.