IL-1β and TNF-α, but not IFN-α, IFN-γ, IL-6 or IL-8, are secretory mediators in human distal colon

Inflammatory bowel disease (IBD) and HIV infection can cause diarrhoea which are 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. Interleukin 1 beta (IL-1 beta) dose dependently increased short-circuit current (I-SC) An I-SC maximum of 2.5 +/- 0.3 mu mol.h(-1).cm(-2) was reached at 20 ng/ml within 43 +/- 4 min. Na-22(+) and Cl-36(-) fluxes were not altered and residual flux increased by 2.4 +/- 1.0 mu mol.h(-1).cm(2) indicating that the IL-l beta-induced I-SC is based on electrogenic bicarbonate secretion. IL-1 beta had no effect on HT-29/B6 epithelial monolayers suggesting that IL-1 beta 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 subepithelial cells in the lamina propria, While tetrodotoxin and the 5-lipoxygenase inhibitor ICI-230487 had no effect, indomethacin completely blocked IL-1 beta action. Prostaglandin determination by RIA revealed an increased production of PGE(2), At half maximum effective concentrations an additive action of tumour necrosis factor alpha (TNF-alpha) could be demonstrated on IL-1 beta-induced secretion. Interferon alpha (IFN-alpha), IFN-gamma, IL-6, and IL-8 had no secretory effect in human distal colon. None of the investigated cytokines altered the intestinal barrier function. By their secretory effects IL-1 beta and TNF-alpha, but not IFN-alpha, IFN-gamma, IL-6, and IL-8, may contribute to diarrhoea in IBD and AIDS. (C) 1998 Academic Press Limited.