MODULATION OF HOST RESPONSE TO ESCHERICHIA-COLI O157/H7 INFECTION BY ANTI-CD18 ANTIBODY IN RABBITS

Background/Aims: Escherichia coli 0157:H7 infection induces diarrhea, severe colitis, and colonic electrolyte transport abnormalities characterized by decreased Na absorption and Cl secretion. The aim of this study was to examine the role of the host inflammatory response in inducing distal colonic transport changes during infection with E. coli 0157:H7. Methods: New Zealand white rabbits aged 10 days were infected with E. coli 0157:H7 strain EDL933 (plasmid+, verotoxin 1+, verotoxin 2+). Studies were performed daily from day 1 to day 5 postinfection and compared with uninfected controls (10 days old). Distal colonic ion transport was studied in vitro under short-circuited conditions in Ussing chambers, and tissue inflammation was assessed by mucosal myeloperoxidase activities and mucosal neutrophil (polymorphonuclear neutrophil [PMN]) counts. In a second study, PMN infiltration was inhibited by an anti-CD18 (leukocyte adhesion molecule) monoclonal antibody, IB4, and histology and transport were studied on day 5 postinfection. Results: Infection with 0157:H7 induced diarrhea and inhibition of Na absorption by day 3. Cl secretion occurred on day 5, coincident with tissue infiltration with PMN. Pretreatment with IB4 prevented histological damage and tissue infiltration with PMN, and it inhibited the transport abnormalities induced by infection alone. Conclusions: Infection with 0157:H7 reduces Na absorption and stimulates Cl secretion in the distal colon. Disruption of the epithelium and changes in colonic electrolyte transport during enterohemorrhagic E. coli are mediated by the host inflammatory response. © 1994.