title: Interleukin 1 beta and tumour necrosis factor alpha inhibit acid secretion in cultured rabbit parietal cells by multiple pathways.
abstract: BACKGROUND
  The cytokines interleukin 1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF-alpha) are inhibitors of gastric acid secretion when administered systemically.
  
  
  OBJECTIVE
  To investigate the inhibitory effect of IL-1 beta and TNF-alpha on cultured, acid secreting parietal cells in order to determine the mechanism of this inhibition.
  
  
  METHODS
  Rabbit parietal cells were prepared by collagenase-EDTA digestion and counter flow elutriation. Acid secretory activity was assessed by aminopyrine accumulation.
  
  
  RESULTS
  IL-1 beta and TNF-alpha inhibited basal and stimulated acid secretion in a dose dependent manner; near maximal effects were seen with both at 10 ng/ml. Inhibition was maximal with 15 minutes pretreatment but seen with up to 18 hours of preincubation. Both cytokines inhibited histamine, carbachol, gastrin, forskolin, and A23187 stimulated acid secretion but had no effect on stimulation by dibutyryl-cAMP. Inhibition of acid secretion was not accompanied by a change in radioligand binding to histamine H2 or gastrin/CCKB receptors. Pertussis toxin abolished the inhibitory effects on histamine and forskolin stimulation. The tyrosine kinase inhibitor herbimycin reduced the inhibitory effects of TNF-alpha against all stimuli but only reduced the effects of IL-1 beta against histamine and forskolin stimulation.
  
  
  CONCLUSIONS
  IL-1 beta and TNF-alpha seem to inhibit parietal cell acid secretion by multiple pathways; the inhibition occurs at postreceptor level and involves pertussis toxin and tyrosine kinase dependent and independent pathways. Mucosal production of cytokines may be important in the regulation of gastric acid secretion.
authors.affiliation: Department of Gastroenterology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
authors.forename: I L
authors.initials: IL
authors.lastname: Beales
authors.forename: J
authors.initials: J
authors.lastname: Calam
mesh_terms: D000818:Animals; D016227:Benzoquinones; D000001:Calcimycin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D018722:Nicotinic Agonists / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000378:metabolism; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D011817:Rabbits; D017828:Rifabutin / Q000031:analogs & derivatives; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D016227:Benzoquinones; D004791:Enzyme Inhibitors; D005755:Gastrins; D007375:Interleukin-1; D007476:Ionophores; D047029:Lactams, Macrocyclic; D018722:Nicotinic Agonists; D011809:Quinones; D014409:Tumor Necrosis Factor-alpha; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D017828:Rifabutin; D000001:Calcimycin; C020754:herbimycin; D006632:Histamine; D002217:Carbachol; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases