Tumour necrosis factor-alpha and interferon-gamma production measured at the single cell level in normal and inflamed human intestine

Abstract

SUMMARY: The spot-ELISA technique has been used to enumerate the frequency of cells secreting tumor necrosis factor-alpha (TNF-α) and interferon-γ (IFN-γ), isolated from biopsies of normal intestine and from biopsies of children with inflammatory bowel disease. TNF-α production was undetectable in six out of 12 biopsies from normal intestine and in the other six biopsies it ranged from 60 to 580 TNF-α-secreting cells/106 isolated intestinal cells. In contrast, cells isolated from biopsies of children with Crohn's disease (n= 9) all showed elevated frequencies of TNF-á-secreting cells (500–12 000 secreting cells/106 cells). In ulcerative colitis, four out of eight children had increased production of TNF-α and in children with indeterminate colitis two out of three had elevated levels. There was no correlation between plasma TNF-α levels and the number of intestinal cells secreting TNF-α. In controls and all groups of patients IFN-γ-secreting cells were uncommon. These results suggest that TNF-α is an important mediator of inflammation in the human gut, and, furthermore, may play a role in the growth failure frequently seen in children with inflammatory bowel disease.