Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. Nov 20, 2015; 5(4): 225-231
Published online Nov 20, 2015. doi: 10.5493/wjem.v5.i4.225
Disease control by regulation of P-glycoprotein on lymphocytes in patients with rheumatoid arthritis
Shizuyo Tsujimura, Yoshiya Tanaka
Shizuyo Tsujimura, Yoshiya Tanaka, the First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu 807-8555, Japan
Author contributions: All the authors contributed to this paper.
Supported by In part by research Grants-In-Aid for Scientific Research by the Ministry of Health, Labor and Welfare of Japan; the Ministry of Education, Culture, Sports, Science and Technology of Japan; University of Occupational and Environmental Health, Japan.
Conflict-of-interest statement: Tanaka Y has received consulting fees, lecture fees, and/or honoraria from Abbvie, Chugai, Astellas, Takeda, Santen, Mitsubishi-Tanabe, Pfizer, Janssen, Eisai, Daiichi-Sankyo, UCB, GlaxoSmithKline, and Bristol-Myers, and has also received research grants from Mitsubishi-Tanabe, Chugai, MSD, Astellas, and Novartis; Dr. Tsujimura S declares no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Yoshiya Tanaka, MD, PhD, Professor, the First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu 807-8555, Japan.
Telephone: +81-93-6031611 Fax: +81-93-6919334
Received: September 13, 2014
Peer-review started: September 13, 2014
First decision: September 28, 2014
Revised: March 7, 2015
Accepted: August 30, 2015
Article in press: August 31, 2015
Published online: November 20, 2015
Core Tip

Core tip: In patients with refractory rheumatoid arthritis (RA) and high disease activity, overexpression of P-glycoprotein (P-gp) on lymphocytes can cause resistance to anti-rheumatic drugs through efflux of intracellular drugs from these cells. Lymphocytes activated by various stimuli, including tumor necrosis factor-α in RA patients apparently acquire P-gp-mediated multidrug resistance against certain anti-rheumatic drugs, which are substrates of P-gp. The use of biological agents that reduce P-gp expression as well as P-gp antagonists can successfully reduce the efflux of drugs from lymphocytes, suggesting that they can be used to overcome drug-resistance and improve clinical outcome.