Increased presence of cells containing transforming growth factor alpha (TGF-alpha) in ulcerative colitis, both during active inflammation and in remission

Objective Patients with extensive and long-standing ulcerative colitis have an increased risk of developing colorectal cancer and sub-epithelial fibro sis. The polypeptide transforming growth factor alpha (TGF-alpha) has mitog enic effects and it is believed that local over-production may result in tu mour formation and fibrosis. Design In the present study, we correlated the presence of TGF-alpha in ulc erative colitis with the degree of inflammation and with dysplasia. Methods Sixty two patients were investigated, 46 with ulcerative colitis (1 6 with active inflammation and 20 in remission, 10 with dysplasia of the co lon), and 16 controls with normal colonoscopy and without a history of coli tis. There were no overlaps between the subgroups. Tissue sections from col onic biopsies were examined and TGF-alpha was detected by immunohistochemis try. TGF-alpha-containing cells were characterized by double-staining with antibodies to eosinophil cationic protein (ECP). An antibody (EG2) recogniz ing eosinophils with an activated phenotype was also used. Results The median number of TGF-alpha-containing cells in the mucosa was 2 4 per mm(2) (inter-quartile range 10-51) in controls, 186 per mm(2) (73-245 ) in ulcerative colitis with active inflammation, 76 per mm(2) (52-198) in remission, and 130 per mm(2) (66-203) in areas of dysplasia. Double-stainin g for TGF-alpha and ECP revealed that most of the TGF-alpha-containing cell s were eosinophils, and most had an activated phenotype as judged by staini ng with EG2. Conclusions The presence of TGF-alpha-containing cells in colonic mucosa is increased both in active inflammation and during remission in ulcerative c olitis. Dysplasia is not associated with any significant increase in TGF-al pha-containing cells. The majority of TGF-alpha-containing cells are eosino phils with an activated phenotype. TGF-alpha released from these cells coul d be important for the development of complications seen in ulcerative coli tis, such as cancer and fibrosis. Eur J Gastroenterol Hepatol 12:761-766 (C ) 2000 Lippincott Williams & Wilkins.