Analysis of enteropathy induced by tumour necrosis factor alpha

Cytokine. 1993 Jan;5(1):24-30. doi: 10.1016/1043-4666(93)90020-6.


Tumour necrosis factor (TNF)-alpha has been implicated in the pathogenesis of experimental and clinical enteropathy, but its exact role is unknown. We show here that a single dose of TNF-alpha causes significant small intestinal pathology in normal adult mice, which develops within 15 minutes, persists for up to 48 hours and is enhanced by interferon-gamma (IFN-gamma). The enteropathy consists of villus atrophy and crypt hyperplasia and is therefore similar to that found in immunologically mediated enteropathies such as graft-versus-host reaction (GvHR). TNF-alpha is also cytotoxic to an intestinal crypt cell line in vitro. Thus, a direct action of TNF-alpha on crypt cells may be involved in its enteropathic effects in vivo. Together, these findings indicate that TNF-alpha alone, or in concert with other cytokines, may be an important effector molecule in immunologically mediated intestinal pathology and may ultimately provide a target for specific immunotherapy for clinical enteropathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Drug Synergism
  • Epithelial Cells
  • Epithelium / drug effects
  • Interferon-gamma / toxicity
  • Intestinal Diseases / chemically induced*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / ultrastructure
  • Leukocyte Count / drug effects
  • Mice
  • Tumor Necrosis Factor-alpha / toxicity*


  • Tumor Necrosis Factor-alpha
  • Interferon-gamma