EXPRESSION OF INTESTINAL DRUG-METABOLIZING-ENZYMES IN PATIENTS WITH CHRONIC INFLAMMATORY BOWEL-DISEASE

The cause of chronic inflammatory bowel disease (IBD) remains unclear, A recent hypothesis suggests that ulcerative colitis may be caused by one or more reactive xenobiotic metabolites. If so, the presence, dis tribution, and activity of drug-metabolizing enzymes in the gut could be important, because those enzymes represent a first defense against ingested xenobiotics. To assess whether patients with IBD express cert ain enzymes differently in the gastrointestinal tract than do subjects without IBD, biopsy samples of the terminal ileum and various regions of the colon were stained immunohistochemically for cytochrome P-450 (CYP) isoenzymes (CYP1A1, CYP2D6, CYP2E1, CYP3A), epoxide hydrolase, a lpha and pi forms of glutsithione-S-transferase (GST), and metallothio nein (MTTH). One hundred fifty biopsy samples from 21 patients with ir ritable colon (no clinical or histologic signs of inflammation; contro l group), 25 patients with crohn's disease (CD), and 37 patients with ulcerative colitis (UC) mere evaluated. The patients' sex, age, smokin g habits, and disease state were not related significantly to the freq uency of positive versus negative staining of the samples. All enzymes were expressed less frequently in the colon than in the terminal ileu m. With the exception of CYP1A1, all enzymes were detectable with simi lar frequency in the three study groups: CYP2E1, 77.4% to 84.6% positi ve stainings; CYP3A, 53.8% to 58.5%; CPP2D6, 23.1% to 36.9%; GST(alpha ), 14.1% to 20.8%; GST(pi), 19.2% to 24.5%; epoxide hydrolase, 1.9% to 3.8% ;and MTTH, 19.2% to 25.4%. However, CYP1A1 staining was positive significantly more often in patients with CD (39.6%) and UC (39.4%) t han in patients in the control group (19.2%). Because cells with CYP1A 1 were found in the intestines of patients with IBD significantly more frequently than in patients in the control group (ie, with an irritab le colon), this may suggest a function of this enzyme in the etiology or pathogenesis of inflammation in these disorders. Alternatively, the more frequent expression of CYP1A1 could be due secondarily to the pr esence of xenobiotics that then lead to inflammation.