Surgically induced leukocytic infiltrates within the rat intestinal muscularis mediate postoperative ileus

Background & Aims: Postoperative ileus is a poorly understood and common pr oblem. We previously demonstrated an association between a suppression in j ejunal circular muscle activity and a massive extravasation of leukocytes i nto the muscularis after surgical manipulation of the small bowel. This stu dy was pursued to establish a direct causal link between these events. Meth ods: Reverse-transcription polymerase chain reaction and immunohistochemist ry were used to detect and localize expression of adhesion molecules: P-sel ectin, intercellular adhesion molecule 1 (ICAM-1), and lymphocyte function- associated antigen 1 (LFA-1). Leukocyte infiltration and in vitro jejunal c ircular muscle function were quantified in controls and manipulated animals with and without antibody treatment (1A29, WT.1, and WT.3). Results: Surgi cal manipulation caused a significant up-regulation within the muscularis o f ICAM-1 and P-selectin messenger RNA. ICAM-1 and P-selectin protein expres sion was increased within the muscularis microvasculature, and ICAM-1 and L FA-1 were expressed on infiltrating cells. Administration of adhesion molec ule antibodies prevented the recruitment of monocytes and neutrophils into the muscularis and also averted jejunal circular muscle dysfunction. Conclu sions: The data demonstrate that adhesion molecule antibodies prevent surgi cally induced suppression of intestinal muscle contractions and therefore s uggests that late postoperative ileus is mediated through a leukocytic infl ammatory response within the intestinal muscularis externa.