Gastroenterology

Gastroenterology

Volume 118, Issue 2, February 2000, Pages 279-288
Gastroenterology

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

https://doi.org/10.1016/S0016-5085(00)70210-1Get rights and content

Abstract

Background & Aims: The multidrug resistance (MDR) gene codes for a drug efflux pump P-glycoprotein 170 (Pgp-170) expressed on the surface of lymphocytes and intestinal epithelial cells. Inflammatory bowel disease (IBD) poorly responsive to medical therapy may relate to MDR expression because glucocorticoids are known Pgp-170 substrates. Methods: Using flow cytometry, we measured peripheral blood lymphocyte (PBL) MDR in 153 IBD patients and 50 healthy volunteers, and assessed the relationship between PBL, mucosal intraepithelial lymphocyte (IEL), and mucosal epithelial cell (EC) MDR expression in a further 20 IBD patients and 19 controls. Results: Compared with controls, 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 who 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 influenced by disease activity or glucocorticoid therapy. Both PBL and mucosal MDR expression appeared independent of disease activity, and there was a significant 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: PBL and mucosal MDR expression may play an important role in determining the response of IBD patients to glucocorticoid therapy.

GASTROENTEROLOGY 2000;118:279-288

Section snippets

Patients

From an IBD database that compiled the clinical records of more than 500 patients with IBD who attended our hospital, we identified 3 patient groups: (1) outpatients with UC who had required a proctocolectomy with an ileoanal pouch (PIAP) in the past for either failed medical therapy or colonic dysplasia; (2) outpatients with CD who had required at least 1 bowel resection in the past for either failed medical therapy or bowel obstruction; and (3) IBD patients who had never required bowel

PBL MDR expression in patients with UC requiring proctocolectomy

The characteristics of the patient with IBD and control population are summarized in Tables 1 and 2.

. Description of UC population

Empty CellPrior surgery (n = 41)No prior surgery (n = 40)Empty Cell
Empty CellFailed treatmentDysplasiaInactiveActiveControls (n = 50)
n2813211950
Age (yr) and sex
 Mean ± SD43.3 ± 15.148.6 ± 17.343.7 ± 18.646.3 ± 16.240.3 ± 12.3
 Range20–7220–7520–7317–7221–62
 Female (%)43%46%43%53%58%
Duration of disease (yr)
 Mean ± SD3.4 ± 5.110.9 ± 8.1b6.8 ± 6.06.9 ± 6.1—
 Range0.1–303–261.2–230.1–31—
Duration

Discussion

The major findings in this study were (1) significantly elevated PBL MDR expression in IBD patients who required surgery several years earlier for failed medical therapy; (2) stable PBL MDR expression among patients with IBD and controls regardless of disease activity or glucocorticoid therapy; and (3) a significant correlation between PBL and colonic mucosal MDR expression among patients with IBD and controls that appeared to be independent of mucosal disease activity.

Some overlap in PBL MDR

Acknowledgements

The authors thank Dr. Alan Kelly, Medical Statistics, Department of Community Health, Trinity College Dublin, for his assistance with the manuscript.

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    ☆

    Address requests for reprints to: Richard J. Farrell, M. D., Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Dana 501, 330 Brookline Avenue, Boston, Massachusetts 02215. e-mail: [email protected]; fax: (617) 667-2767.

    ☆☆

    Drs. Farrell and Donnelly were recipients of Health Research Board research fellowships, Aideen Long was a recipient of a Wellcome Trust Career Development Award, and for part of the period of the study Dr. Dermot Kelleher was a Wellcome Senior Fellow in Clinical Science.

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