title: H2 blockers decrease gut mucus production and lead to barrier dysfunction in vitro.
abstract: BACKGROUND
  Pneumonia 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.
  
  
  METHODS
  HT29-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.
  
  
  RESULTS
  Cimetidine 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.
  
  
  CONCLUSIONS
  Cimetidine 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.
authors: Department of Surgery, Wayne State University, Detroit, MI 48201, USA. ldiebel@med.wayne.edu
authors: Lawrence N
authors: LN
authors: Diebel
authors: David M
authors: DM
authors: Liberati
authors: Lisa
authors: L
authors: Hall-Zimmerman
mesh_terms: D001422:Bacterial Adhesion / Q000187:drug effects; D002927:Cimetidine / Q000009:adverse effects; D016638:Critical Illness; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology; D019073:HT29 Cells; D006635:Histamine H2 Antagonists / Q000009:adverse effects*; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000382:microbiology / Q000503:physiopathology*; D009077:Mucins / Q000096:biosynthesis; D009093:Mucus / Q000187:drug effects* / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D006635:Histamine H2 Antagonists; C508600:IL6 protein, human; D015850:Interleukin-6; D009077:Mucins; D014409:Tumor Necrosis Factor-alpha; D002927:Cimetidine