Challenge of rabbit intestinal loops with Salmonella typhimurium or Vibrio cholerae resulted in significant elevation of mucosal cyclic adenosine monophosphate (cAMP) and prostaglandin concentrations. This effect could be reproduced in vitro by exposing either isolated epithelial cells from normal rabbits or Chinese hamster ovary cells to purified cholera toxin or cell-free lysates of Salmonella. Indomethacin treatment of animals challenged with Salmonella resulted in less fluid accumulation, in addition to lower concentrations of intestinal cAMP and prostaglandins, compared to that of similarly changed loops in normal animals. Likewise, intestinal loop challenge of indomethacin-treated rabbits with V. cholerae or purified cholera toxin also resulted in decreased fluid secretion and diminished levels of tissue cAMP and prostaglandins. Intestinal loop tissue from normal animals challenged with V. cholerae displayed 10-fold higher levels of prostaglandins than tissue from uninfected animals. Prostaglandin levels in Salmonella-infected intestinal loops were similarly elevated, but by only 2-3 fold. Chinese hamster ovary cell monolayers were simultaneously exposed to either 10 ng of cholera toxin or 20 μl of Salmonella lysate and varying concentrations of indomethacin ranging from 1 ng/ml to 10 μg/ml. Indomethacin decreased both cAMP and prostaglandin levels in Chinese hamster ovary cells. At high indomethacin concentrations, the cells lost their ability to respond to stimulation with either cholera toxin or Salmonella lysate, while retaining greater than 95% viability as determined by trypan blue exclusion. The prostaglandind and cAMP content of epithelial cells from Salmonella-challenged loops was increased in crypt epithelial cell fractions. Prostaglandin concentrations were elevated in isolated intestinal epithelial cells exposed to purified cholera toxin in vitro. These data indicate that prostaglandins synthesized by the epithelial cells are involved in the pathogenesis of both experimental cholera and salmonellosis. The data are consistent with an enterotoxin-mediated mechanism for both diarrheal diseases and argue against the role of inflammatory cells as the source of elevated cAMP and prostaglandins appearing in the intestinal mucosa during experimental salmonellosis.
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