title: Modulation of cytokine release from colonic explants by bacterial antigens in inflammatory bowel disease.
abstract: The intestinal flora play an important role in experimental colitis and inflammatory bowel disease (IBD). Using colonic explant cultures from 132 IBD and control subjects, we examined tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 and interleukin-1 receptor antagonist (IL-1RA) production in vitro in response to bacterial activators. Unstimulated TNF-alpha release was increased significantly in rectal biopsies from involved IBD tissue, correlating with inflammation severity. Whereas lipopolysaccharide (LPS) only moderately stimulated TNF-alpha production from inflamed tissue, pokeweed mitogen (PWM) induced its release in all groups, with a stronger response in involved IBD tissue. Superantigen staphylococcal enterotoxin A (SEA) had a similar, but weaker effect. SEB was observed to be the strongest inducer of TNF-alpha for all groups, again with a more marked response in inflamed tissue. Stimulated release of IL-1 was considerably less than for TNF-alpha. The superantigens' superior potency over LPS was not as marked for IL-1 as it was for TNF-alpha. In addition to IL-1, IL-1RA release was also triggered by the bacterial products. The net effect of activation on the IL-1RA/IL-1 ratio was relatively modest. Release of the proinflammatory cytokines TNF-alpha and IL-1, as well as that of the anti-inflammatory cytokine IL-1RA was increased by incubation of colonic tissue with bacterial factors. TNF-alpha production and release was increased significantly in involved colonic explants from IBD. SEB was even capable of inducing TNF-alpha release from uninvolved colonic tissue.
authors.affiliation: Mucosal Immunology Laboratory, Research Center, Ste-Justine Hospital, Departments of Pediatrics and Nutrition, Université de Montreal, Montreal, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Dionne
authors.forename: S
authors.initials: S
authors.lastname: Laberge
authors.forename: C
authors.initials: C
authors.lastname: Deslandres
authors.forename: E G
authors.initials: EG
authors.lastname: Seidman
mesh_terms: D000293:Adolescent; D000942:Antigens, Bacterial / Q000494:pharmacology*; D016022:Case-Control Studies; D002648:Child; D003093:Colitis, Ulcerative / Q000276:immunology; D003106:Colon / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D004768:Enterotoxins / Q000494:pharmacology; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007375:Interleukin-1 / Q000032:analysis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009924:Organ Culture Techniques; D011043:Pokeweed Mitogens / Q000494:pharmacology; D017472:Receptors, Interleukin-1 / Q000032:analysis / Q000037:antagonists & inhibitors; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D004768:Enterotoxins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011043:Pokeweed Mitogens; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; C026066:enterotoxin A, Staphylococcal