Review The role of adenosine receptors in rheumatoid arthritis Katia Varani a,1 , Melissa Padovan b, ⁎ ,1 , Marcello Govoni b , Fabrizio Vincenzi a , Francesco Trotta b , Pier Andrea Borea a a Department of Clinical and Experimental Medicine, Pharmacology Section, University of Ferrara, Ferrara, Italy b Department of Clinical and Experimental Medicine, Rheumatology Section, University of Ferrara and Sant'Anna Hospital, Azienda Ospedaliero-Universitaria di Ferrara, Ferrara, Italy abstract article info Article history: Received 20 July 2010 Accepted 28 July 2010 Available online 5 August 2010 Keywords: Rheumatoid arthritis Adenosine Adenosine receptors Inflammation Rheumatoid arthritis (RA), is the most common inflammatory musculoskeletal disease inducing diminished quality-of-life in the affected individuals and having major impact on society due to decrease work ability. Early diagnosis and immediate, effective therapy are crucial in order to prevent unfavorable outcome. Treatment of RA has progressed during the past two decades thanks to the advent of a large number of new agents targeting different specific molecules and pathways involved in the modulation of the inflammation. In this scenario an important role is covered by adenosine, a purine nucleoside released from a variety of cells in response to metabolic and inflammatory stress, which is considered to be a potent endogenous regulator acting through its interaction with 4 cell surface receptors named as A 1 ,A 2A ,A 2B and A 3 . Adenosine receptor stimulation has complex effects on the release of pro-inflammatory cytokines depending on selective receptor engagement. Recent data show the involvement of adenosine pathways in RA and its potential therapeutic implications. © 2010 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 2. Rheumatoid Arthritis: background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 3. Adenosine and adenosine receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 4. Adenosine receptors and the regulation of inflammation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 5. Novel pharmacological target therapies in RA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 6. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Disclosure statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 Take-home messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 1. Introduction The pathophysiology of rheumatic inflammatory disorders and systemic autoimmune diseases is not yet fully understood. Rheuma- toid arthritis (RA) is one of the most important chronic, progressive and disabling inflammatory diseases characterized by joint destruc- tive process associated with synovial proliferation and secretion of high levels of pro-inflammatory mediators including cytokines and growth factors. Early diagnosis and early effective therapy are crucial in order to prevent unfavorable outcome with joint deterioration and functional disability. Currently, optimal management of RA is needed within 3–6 months after the onset of disease, since a narrow “window of opportunity” is considered to be suitable to achieve remission. Early prognostic assessment in order to establish the risk of aggressive disease and radiological progression is critical to guide the most appropriated therapeutic approach. Significant amount of data have become available suggesting that genetic factors and inflammatory biomarkers are good predictors of outcome enabling a careful profiling of both patients and disease. New therapeutic approaches aimed to modulate inflammation and to prevent joint damage are now under investigation. Adenosine, a well known purine nucleoside, interacting with 4 types of cell surface G-protein-coupled adenosine Autoimmunity Reviews 10 (2010) 61–64 ⁎ Corresponding author. Rheumatology Section, Department of Clinical and Experimental Medicine, University of Ferrara, C.so Giovecca 203, 44100 Ferrara, Italy. Tel.: +39 0532 236314; fax: +39 0532 207221. E-mail address: melipadovan@yahoo.it (M. Padovan). 1 These authors contributed equally to this work. 1568-9972/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.autrev.2010.07.019 Contents lists available at ScienceDirect Autoimmunity Reviews journal homepage: www.elsevier.com/locate/autrev