IL-1beta and TNF-alpha, but not IFN-alpha, IFN-gamma, IL-6 or IL-8, are secretory mediators in human distal colon

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. 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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chlorides / metabolism
  • Colon / drug effects
  • Colon / metabolism*
  • Cyclooxygenase Inhibitors
  • Cytokines / administration & dosage
  • Cytokines / pharmacology*
  • Dinoprostone / metabolism
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Enteric Nervous System / drug effects
  • Enteric Nervous System / physiology
  • Humans
  • In Vitro Techniques
  • Indomethacin / pharmacology
  • Interferon-alpha / pharmacology
  • Interferon-gamma / administration & dosage
  • Interferon-gamma / pharmacology
  • Interleukin-1 / administration & dosage
  • Interleukin-1 / pharmacology*
  • Interleukin-6 / pharmacology
  • Interleukin-8 / pharmacology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Ion Transport / drug effects
  • Ion Transport / physiology*
  • Lipoxygenase Inhibitors / pharmacology
  • Pyrans / pharmacology
  • Quinolones / pharmacology
  • Radioimmunoassay
  • Sodium / metabolism
  • Tetrodotoxin / pharmacology
  • Time Factors
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Tumor Necrosis Factor-alpha / pharmacology


  • Chlorides
  • Cyclooxygenase Inhibitors
  • Cytokines
  • Interferon-alpha
  • Interleukin-1
  • Interleukin-6
  • Interleukin-8
  • Lipoxygenase Inhibitors
  • Pyrans
  • Quinolones
  • Tumor Necrosis Factor-alpha
  • ZM 230487
  • Tetrodotoxin
  • Interferon-gamma
  • Sodium
  • Dinoprostone
  • Indomethacin