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MDR1 mRNA Expressions in Peripheral Blood Mononuclear Cells of Patients with Ulcerative Colitis in Relation to Glucocorticoid Administration

From the Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan (Dr. Hirano, K. Onda, T. Toma, Dr. Oka); Gastroenterology Department of Internal Medicine, Hachioji Medical Center, Tokyo, Japan (Dr. Miyaoka); and 4th Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan.

Overexpression of multidrug resistance (MDR) protein, P-glycoprotein (P-gp), on lymphocytes has been suggested to be implicated in the failure of glucocorticoid (GC) therapy in patients with ulcerative colitis (UC). However, whether the overexpression of P-gp in a class of patients with inflammatory bowel disease (IBD) is intrinsic or related to the administration of GC is unknown. Relative amounts of MDR1 mRNA expressed in peripheral blood mononuclear cells (PBMCs) were measured using the reverse-transcriptase polymerase chain reaction (RT-PCR) technique in 25 UC patients having no history of GC administration, 25 UC patients having experienced GC therapy, 19 patients with Crohn's disease (CD) with no history of GC therapy, and 27 healthy subjects. Relative amounts of MDR1 mRNA expressed in PBMCs were compared among the groups. The relationship between the amounts of MDR1 mRNA expressed, as well as the total dose of GC administered or the period of GC therapy in UC patients, was examined. The relative amounts of MDR1 mRNA expressed in PBMCs were not significantly different between the healthy subjects and CD patients or UC patients having no history of GC therapy. However, the mean MDR1 mRNA amount in PBMCs of UC patients having experienced GC therapy was significantly greater than that in PBMCs of UC patients with no history of GC administration (p = 0.0375). The amounts of MDR1 mRNA in PBMCs of UC patients having experienced GC therapy significantly correlated with the total dose of GCs administered (p = 0.0175). Overexpression of MDR1 mRNA in PBMCs of IBD patients is not intrinsic. However, high-dose administration of GCs for the treatment of UC may result in an increased expression of MDR1 mRNA, which may impair successful GC therapy in these patients.

Key Words: P-glycoprotein • glucocorticoid therapy • ulcerative colitis • inflammatory bowel disease • peripheral blood mononuclear cells

Address for reprints: Toshihiko Hirano, PhD, Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.

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