Bode H, Schmitz H, Fromm M, Scholz P, Riecken E O, Schulzke J D
Department of Gastroenterology, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, D-12200 Berlin, Germany.
Cytokine. 1998 Jun;10(6):457-65. doi: 10.1006/cyto.1997.0307.
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.
炎症性肠病（IBD）和HIV感染可导致腹泻，并伴有细胞因子水平升高。为阐明细胞因子的致病作用，采用尤斯灌流技术在人远端结肠研究了它们对离子分泌的影响。白细胞介素1β（IL-1β）剂量依赖性增加短路电流（ISC）。在20 ng/ml时，43±4分钟内ISC最大值达到2.5±0.3 μmol·h-1·cm-2。22Na+和36Cl-通量未改变，残余通量增加2.4±1.0 μmol·h-1·cm-2，表明IL-1β诱导的ISC基于电生性碳酸氢盐分泌。IL-1β对HT-29/B6上皮单层无影响，提示IL-1β不直接作用于上皮细胞。此外，在人结肠中，去除黏膜下层（完全剥离）后该作用未减弱，表明通过固有层上皮下细胞存在一个介导步骤。虽然河豚毒素和5-脂氧合酶抑制剂ICI-230487无作用，但吲哚美辛完全阻断IL-1β的作用。通过放射免疫分析法测定前列腺素显示PGE2产生增加。在半数最大有效浓度时，可证明肿瘤坏死因子α（TNF-α）对IL-1β诱导的分泌有相加作用。干扰素α（IFN-α）、IFN-γ、IL-6和IL-8在人远端结肠无分泌作用。所研究的细胞因子均未改变肠道屏障功能。通过其分泌作用，IL-1β和TNF-α而非IFN-α、IFN-γ、IL-6和IL-8可能导致IBD和艾滋病中的腹泻。
