IL-1beta and TNF-alpha, but not IFN-alpha, IFN-gamma, IL-6 or IL-8, are secretory mediators in human distal colon.
Inflammatory bowel disease (IBD) and HIV infection can cause diarrhoea which is accompanied by elevated cytokine levels. To elucidate a pathogenic role of cytokines, their effect on ion secretion was studied in human distal colon using the Ussing technique. Interluekin 1beta (IL-1beta) dose dependently increased short-circuit current (ISC). An ISC maximum of 2.5+/-0.3 micromol. h-1.cm-2 was reached at 20 ng/ml within 43+/-4 min. 22Na+ and 36Cl- fluxes were not altered and residual flux increased by 2.4+/-1.0 micromol.h-1.cm-2 indicating that the IL-1beta-induced ISC is based on electrogenic bicarbonate secretion. IL-1beta had no effect on HT-29/B6 epithlial monolayers suggesting that IL-1beta does not act directly on the epithelium. Furthermore, in human colon the effect was not attenuated by removal of the submucosa (total stripping) pointing to a mediation step via subepithlial cells in the lamina propria. While tetrodotoxin and the 5-lipoxygenase inhibitor ICI-230487 had no effect, indomethacin completely blocked IL-1beta action. Prostaglandin determination by RIA revealed an increased production of PGE2. At half maximum effective concentrations an additive action of tumour necrosis factor alpha (TNF-alpha) could be demonstrated on IL-1beta-induced secretion. Interferon alpha (IFN-alpha), IFN-gamma, IL-6, and IL-8 had no seretory effect in human distal colon. None of the investigated cytokines altered the intestinal barrier function. By their secretory effects IL-1beta and TNF-alpha, but not IFN-alpha, IFN-gamma, IL-6, and IL-8, may contribute to diarrhoea in IBD and AIDS.
Bode
H
H
Department of Gastroenterology, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, D-12200 Berlin, Germany.
Schmitz
H
H
Fromm
M
M
Scholz
P
P
Riecken
E O
EO
Schulzke
J D
JD
D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines / Q000008:administration & dosage / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D017615:Enteric Nervous System / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D011714:Pyrans / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D011863:Radioimmunoassay; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology
D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D016898:Interferon-alpha; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D016859:Lipoxygenase Inhibitors; D011714:Pyrans; D015363:Quinolones; D014409:Tumor Necrosis Factor-alpha; C088450:ZM 230487; D013779:Tetrodotoxin; D007371:Interferon-gamma; D012964:Sodium; D015232:Dinoprostone; D007213:Indomethacin