leukotriene-b4 and Ileal-Diseases

In order to evaluate its possible role in the pathogenesis of pouchitis we measured the release, into the incubation medium of leukotriene B4 from mucosal samples from patients with ileal pouch-anal anastomosis and correlated release with clinical, endoscopic and histological features.. Leukotriene B4 release was significantly elevated in patients with active pouchitis in comparison to those with a normal pouch mucosa (P < 0.007). No overlap was observed between leukotriene B4 levels from patients with active pouchitis samples and those obtained from individuals without pouchitis. Effective treatment of pouchitis was associated with a significant reduction in leukotriene B4 mucosal release to the incubation medium (P < 0.03). However, even in remission, levels of leukotriene B4 release remained significantly increased in these patients in comparison to people who never experienced pouchitis (P < 0.003). A modest correlation was observed between pouchitis disease activity index and leukotriene B4 release (r = 0.596; P < 0.01).. These results suggest that the increased production of leukotriene B4 may be implicated in the pathogenesis of pouchitis. The persistence of an increased mucosal release of leukotriene B4 in pouchitis patients during clinical remission suggests the presence of a chronic, ongoing, underlying inflammatory process.

Topics: Adult; Case-Control Studies; Colitis, Ulcerative; Female; Humans; Ileal Diseases; Inflammatory Bowel Diseases; Intestinal Mucosa; Leukotriene B4; Male; Middle Aged; Postoperative Complications; Proctocolectomy, Restorative; Severity of Illness Index; Statistics, Nonparametric

Clostridium difficile toxin A is the principal mediator of inflammatory enterocolitis in experimental animals. The purpose of this study was to explore the effect of ketotifen, an anti-inflammatory drug, on toxin A-induced enterotoxicity in rat ileum.. The effects of intragastric administration of ketotifen on secretion, mannitol permeability, histological damage, and mucosal levels of leukotriene B4, leukotriene C4, and platelet activating factor in toxin A-exposed rat ileal loops were measured in vivo. The effects of ketotifen on toxin A-mediated release of rat mast cell protease II (rat mucosa mast cell product) release were also measured in rat ileal explants in vitro. The effect of ketotifen on neutrophil migration in vitro was also evaluated.. Ketotifen pretreatment inhibited toxin A-associated intestinal secretion by 42.5% and mannitol permeability by 56.3% and reduced epithelial cell inflammation and necrosis. These effects were associated with reduced levels of leukotriene B4 by 65.8%, leukotriene C4 by 88.8%, platelet activating factor by 77.8%, and inhibition of rat mast cell protease II by 58.4%. In addition, pretreatment of neutrophils with ketotifen inhibited neutrophil migration in vitro.. The protective effect of ketotifen in this animal model was associated with significant inhibition of release of mast cells and neutrophil derived mediators, supporting their involvement in C. difficile enteritis.

Topics: Animals; Bacterial Toxins; Chemotaxis, Leukocyte; Endopeptidases; Enteritis; Enterotoxins; Ileal Diseases; Ileum; Intestinal Mucosa; Ketotifen; Leukotriene B4; Male; Mannitol; Mast Cells; Neutrophils; Permeability; Platelet Activating Factor; Rats; Rats, Wistar; SRS-A