High multidrug resistance (P-glycoprotein 170) expression in inflammatory bowel disease patients who fail medical therapy

Background & Aims: The multidrug resistance (MDR) gene codes for a drug eff lux pump P-glycoprotein 170 (Pgp-170) expressed on the surface of lymphocyt es and intestinal epithelial cells. Inflammatory bowel disease (IBD) poorly responsive to medical therapy may relate to MDR expression because glucoco rticoids are known Pgp-170 substrates. Methods: Using flow cytometry, we me asured peripheral blood lymphocyte (PBL) MDR in 153 IBD patients and 50 hea lthy volunteers, and assessed the relationship between PBL, mucosal intraep ithelial lymphocyte (IEL), and mucosal epithelial cell (EC) MDR expression in a further 20 IBD patients and 19 controls. Results: Compared with contro ls, PBL MDR was significantly elevated in patients with Crohn's disease who required bowel resection for failed medical therapy (mean +/- SEM, 26.7 +/ - 2.8 vs. 11.9 +/- 1.0; P < 0.0001) and patients with ulcerative colitis wh o required proctocolectomy for failed medical therapy (20.3 +/- 2.5 vs. 11. 9 +/- 1.0; P = 0.001). PBL MDR remained stable over time and was not influe nced by disease activity or glucocorticoid therapy. Both PBL and mucosal MD R expression appeared independent of disease activity, and there was a sign ificant correlation between PBL MDR expression and both IEL expression (r = 0.92; P < 0.0001) and EC expression (r = 0.54; P < 0.001). Conclusions: PB L and mucosal MDR expression may play an important role in determining the response of IBD patients to glucocorticoid therapy.