Multidrug resistance proteins in rheumatoid arthritis, role in disease-modifying antirheumatic drug efficacy and inflammatory processes: an overview

Drug resistance is generally accepted as an important cause of treatment failure for patients with neoplastic or infectious diseases. Molecular mechanisms underlying drug resistance include the action of drug efflux pumps belonging to the super-family of ATP binding cassette (ABC) proteins, which mediate the cellular extrusion of a large variety of therapeutic drugs, a phenotype that is referred to as multidrug resistance (MDR). Unlike neoplastic and infectious diseases, chronic inflammatory diseases have received little attention. The potential role of ABC transporters in determining the efficacy of anti-rheumatic drugs, notably disease modifying anti-rheumatic drugs (DMARDs), in patients with rheumatoid arthritis is unclear. Based on knowledge from the field of oncology and immunology, this review concentrates on the pharmacological role of MDR proteins in the (clinical) efficacy of several DMARDs, as well as the physiological role of MDR proteins in transporting signalling molecules important in inflammatory processes.