Tumor necrosis factor-alpha in ileal mast cells in patients with Crohn's disease.
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.


OBJECTIVE
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).


CONCLUSIONS
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.
Lilja
I
I
Department of Biomedicine and Surgery, Division of Surgery, Linköping University, Faculty of Health Sciences, Linköping, Sweden.
Gustafson-Svärd
C
C
Franzén
L
L
Sjödahl
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D002452:Cell Count; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007079:Ileitis / Q000378:metabolism / Q000473:pathology; D007082:Ileum / Q000378:metabolism* / Q000473:pathology; D007124:Immunoenzyme Techniques; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha