Increased presence of eosinophilic granulocytes expressing transforming growth factor-beta1 in collagenous colitis

BACKGROUND: Collagenous colitis is a disease characterized by chronic watery diarrhea, and on microscopic examination of colonic tissue, a typical thickening of the subepithelial collagen layer is seen. The etiology and pathophysiology behind this disease state are largely unknown. METHODS: We have used in situ hybridization and immunohistochemistry to study the expression of transforming growth factor (TGF) -beta1, a growth factor with the capacity to cause accumulation of collagen in tissues, in collagenous colitis. Colonic pinch biopsy specimens from a total of 34 patients were investigated: 17 patients with collagenous colitis and 17 controls. RESULTS: In patients with collagenous colitis there was increased expression of the TGF-beta1 gene compared with controls, as visualized by in situ hybridization. The vast majority of the TGF-beta1-expressing cells were eosinophils, both in collagenous colitis and controls, but there were also scattered fibroblastic and histiocytic stromal cells. Immunohistochemistry showed the presence of TGF-beta1, mainly in eosinophils, in the colonic mucosa. Morphometric quantification showed 603 +/- 192 eosinophils/mm2, (mean +/- standard error of the mean) in the colonic mucosa of patients with collagenous colitis compared with 30 +/- 7 eosinophils/mm2 in the controls. CONCLUSIONS: The present results suggest that eosinophils expressing TGF-beta1 may be of pathophysiologic importance in the connective tissue remodeling seen in collagenous colitis.