Modulation of cytokine release from colonic explants by bacterial antigens in inflammatory bowel disease.
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.
Dionne
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Mucosal Immunology Laboratory, Research Center, Ste-Justine Hospital, Departments of Pediatrics and Nutrition, Université de Montreal, Montreal, Canada.
Laberge
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Deslandres
C
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Seidman
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EG
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
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