Importance of the intestinal inflammatory reaction in salmonella-mediated intestinal secretion

The ability of Salmonella typhimurium to invade the intestinal epithelium is essential to the pathogenesis of salmonella-induced intestinal secretion. This invasion is accompanied by an intense acute inflammatory reaction. The present study tests the hypothesis that the acute inflammatory reaction may have a role in the pathogenesis of salmonella-induced secretion. Two groups of rabbits infected with S. typhimurium were studied: normal animals and animals pretreated with nitrogen mustard. Nitrogen mustard depletes the polymorphonuclear leukocyte pool and thereby prevents the formation of an acute inflammatory reaction. In vivo ligated ileal loops were constructed and infected 72 h after nitrogen mustard administration when polymorphonuclear leukocytes were undetectable. Nitrogen mustard treatment markedly inhibited salmonella-induced secretion. Ileal histology in normal animals infected with S. typhimurium revealed an intense acute inflammatory reaction, while in animals pretreated with nitrogen mustard only a rare polymorphonuclear leukocyte was seen. The antisecretory effect of nitrogen mustard was not merely a nonspecific effect since nitrogen mustard treatment did not inhibit cholera toxin-induced secretion and did not alter either ileal morphology nor the activities of various intestinal enzymes in normal animals. Nitrogen mustard also did not alter the virulence of the inoculated S. typhimurium. These data suggest that the mucosal inflammatory reaction induced by salmonella invasion may be important to the pathogenesis of the salmonella secretory process. The mechanism by which the inflammatory reaction stimulates secretion is not known.