H2 blockers decrease gut mucus production and lead to barrier dysfunction in vitro

BackgroundPneumonia and other gut-related infectious complications have been associated with the use of histamine 2 (H2) receptor antagonists such as cimetidine in critically ill patients. The mechanism(s) may include acid suppression with resultant effects on the gut flora. Other possibilities include immunologic effects and perturbation of gut barrier function. Recent work has demonstrated the importance of mucus on the gastrointestinal mucosal barrier. We studied the effect of cimetidine on mucus production and mucosal barrier function in vitro.MethodsHT29–MTX, a mucus-producing intestinal epithelial cell line, was used. HT29–MTX cell monolayers were grown to confluence in the presence of cimetidine for 0, 3, or 6 days. Mucus production was quantified by Western Blot analysis and O-linked oligosaccharide chain release and mucin content by enzyme-linked immunosorbent assay. Fluorescein-labeled Escherichia coli (EC) or unlabeled EC were added to quantify bacterial adherence (60-min co-culture) and passage thru HT29–MTX cell monolayers (120-min co-culture), respectively.ResultsCimetidine treatment decreased mucus/mucin content after 3 or 6 days of treatment. The effect was more profound after 6 days. There was nearly a 2-fold increase in passage of EC across HT29–MTX monolayers after cimetidine treatment.ConclusionCimetidine seems to contribute to gut barrier dysfunction by its effect on mucus production. This study supports the increasing clinical suspicion that routine administration of H2 blockers in critically ill patients may be ill advised.