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Tumor necrosis factor-alpha in ileal mast cells in patients with Crohn's disease
I Lilja1, C Gustafson-Svärd, L Franzén
1Department of Biomedicine and Surgery, Division of Surgery, Linköping University, Faculty of Health Sciences, Linköping, Sweden.
Background:
Reports that both intestinal and extraintestinal Crohn's disease (CD) had healed successfully after treatment with anti-tumor necrosis factor-alpha (TNF-alpha) antibody have strengthened the hypothesis that it has a role in the treatment of CD. The macrophage is one source of TNF-alpha. Intestinal mast cells are also thought to have a role in CD, but it is not known if human ileal mast cells express TNF-alpha.
Aim:
To find out whether TNF-alpha is expressed by mast cells in the ileal wall in CD patients and controls.
Methods:
TNF-alpha was sought immunohistochemically in full thickness specimens of ileal wall from patients with CD (histologically normal, n = 9; inflamed, n = 6) and controls (patients with colonic cancer, n = 8). Mast cells were identified by metachromasia and anti-mast cell tryptase immunoreactivity.
Results:
In all layers of the ileal wall, and in every specimen investigated, mast cells were the main cell type that expressed TNF-alpha immunoreactivity out of the TNF-alpha-labelled cells. The number of TNF-alpha- labelled mast cells was greater in the muscularis propria in patients compared with controls, both in uninflamed (1.7-fold, p < 0.05) and in inflamed bowel (4.6-fold, p < 0.002); greater in the submucosa in inflamed compared with uninflamed CD (1.6-fold, p < 0. 01), and less in the lamina propria in inflamed compared with uninflamed CD (0.4-fold, p < 0.05).
Conclusion:
Mast cells are an important source of TNF-alpha in all layers of the ileal wall, and the increased density of TNF-alpha-positive mast cells in the submucosa and muscularis propria may contribute to the tissue changes and symptoms in CD.