Suramin ameliorates collagen induced arthritis Debasis Sahu a, b , Ashish Saroha a, c , Saugata Roy a , Sandip Das d, 1 , Prem S. Srivastava b , Hasi R. Das a, ⁎ a Genomics and Molecular Medicine, Institute of Genomics and Integrative Biology (CSIR), Mall Road, Delhi-110 007, India b Department of Biotechnology, Faculty of Science, Jamia Hamdard, New Delhi-110 062, India c Department of Natural Sciences, West Bengal University of Technology, Salt lake, Kolkata-700 064, India d Department of Botany, Delhi University, Delhi-110 007, India abstract article info Article history: Received 10 June 2011 Received in revised form 28 November 2011 Accepted 1 December 2011 Available online 14 December 2011 Keywords: Suramin Anti-inflammatory Pro-inflammatory cytokine Glycoprotein Collagen-induced arthritis Suramin, a polysulfonated polyaromatic symmetrical urea is known for multiple therapeutic effects including antineoplastic activity. It is known as an antagonist of ATP at P2X purinergic receptors. Suramin is also found to inhibit protein synthesis affecting both initiation and elongation of the polypeptide chain. As a growth factor blocker, it is reported to suppress experimental myocardial inflammation. Here, we describe the anti-arthritic property of suramin in the collagen induced arthritic (CIA) rat, a model of human rheumatoid arthritis (RA). Intraperitoneal (i.p) injection of suramin (10 mg/kg/day) for 3 weeks was found to reduce in- flammation and repair joint destruction in CIA rats. Recovery of body weight (p b 0.0001), reduction in splenic (p b 0.05) and arthritic indices (p b 0.0001) and reappearance of smooth synovial lining after suramin treat- ment to CIA rats were found to be significant. Levels of pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 in plasma and joint extracts were reduced (p b 0.0001) significantly in response to suramin treat- ment. Several acute phase proteins were normalized after suramin administration. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Suramin, has been widely used to treat trypanosomiasis, oncho- cerciasis [1,2] and is being evaluated as an anticancer drug [3]. It is an agent with broad-spectrum biological effects, including the ability to in- hibit the binding of growth factors to their receptors, glycosaminoglycan degradation, membrane-associated ion pumps, protein kinase C, glycoly- sis, and cell motility [4]. Suramin is known to have anti-tumor necrosis factor (TNF)-α activity [5]. TNF-α is a critical pleiotropic cytokine and its overproduction has been implicated in the pathogenesis of a number of inflammatory diseases including rheumatoid arthritis (RA) [6–10]. As a potential debilitating, chronic autoimmune disease, RA mainly affects joints, characterized by synovial hyperplasia, inflammatory cell recruitment, and progressive destruction of cartilage and bone. Al- though the etiology of RA is still unclear, the sequence of events in the disease pathogenesis and the end-stage effector mechanisms are well established [11,12]. Processes like mononuclear cell infiltration, synthesis of an array of degradative enzymes and production of inflam- matory mediators like TNF-α, interleukin (IL)-1β and IL-6 result in joint damage [13]. The use of TNF-α and IL-1β antagonists in RA patients have shown substantial efficacy, but entails high cost, hypersensitiv- ity to medications and infections [14]. The therapeutic effects in rheumatic diseases might be achieved by antagonizing additional pro-inflammatory cytokines, including TNF-α. Suramin has been demonstrated to impart its anti-TNF-α activity by promoting the dis- sociation of the biologically active trimeric form of TNF-α into inac- tive subunits, thus inhibiting the binding of TNF-α to its cellular receptors [5,15,16]. Suramin is also known to block the activity of IL-6 as it interferes with binding to its cell surface receptors [17]. It also has anti-inflammatory properties as it suppresses myocardial inflammation in experimental autoimmune myocarditis (EAM) [18]. The effects of suramin in ameliorating arthritic conditions are not yet studied; assuming that suramin is a partial TNF-α blocker, the present study was undertaken. Collagen induced arthritis (CIA), a well established animal model of RA, is frequently used to test new therapeutics [19,20]. The CIA model shares many pathophysiological properties with human RA, such as severe inflammation, mononuclear cell infiltration and carti- lage and bone destruction [19]. The purpose of this study was to examine whether administration of suramin could exert a therapeutic effect on CIA in experimental animals. 2. Materials and methods 2.1. Materials General laboratory reagents including suramin were purchased from Sigma Aldrich Chem., St. Louis, MO (USA), porcine type II International Immunopharmacology 12 (2012) 288–293 ⁎ Corresponding author at: Genomics and Molecular Medicine, Institute of Genomics and Integrative Biology, Delhi University Campus, Mall Road, Delhi-110 007, India. Tel.: + 91 11 27662581; fax: + 91 11 27667471. E-mail addresses: devashish_2583@yahoo.co.in (D. Sahu), ashishsaroha@gmail.com (A. Saroha), saugat.2001@gmail.com (S. Roy), sd66@rediffmail.com (S. Das), pss410@rediffmail.com (P.S. Srivastava), hdas@igib.res.in, hasidas@yahoo.com (H.R. Das). 1 Present address. 1567-5769/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.intimp.2011.12.003 Contents lists available at SciVerse ScienceDirect International Immunopharmacology journal homepage: www.elsevier.com/locate/intimp