High multidrug resistance (P-glycoprotein 170) expression in inflammatory bowel disease patients who fail medical therapy.
OBJECTIVE
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.
Farrell
R J
RJ
Sir Patrick Dun's Research Laboratory, Trinity College Dublin, St James's Hospital, Ireland. rfarrell@caregroup.harvard.edu
Murphy
A
A
Long
A
A
Donnelly
S
S
Cherikuri
A
A
O'Toole
D
D
Mahmud
N
N
Keeling
P W
PW
Weir
D G
DG
Kelleher
D
D
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000235:genetics; D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D003082:Colectomy; D003106:Colon / Q000276:immunology / Q000473:pathology; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D019450:Genes, MDR; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery / Q000628:therapy*; D007413:Intestinal Mucosa / Q000276:immunology / Q000503:physiopathology; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D012016:Reference Values; D017211:Treatment Failure
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005938:Glucocorticoids; D019804:Mesalamine; D016572:Cyclosporine; D001379:Azathioprine; D008727:Methotrexate