Changes in matrix metalloproteinases and their inhibitors during interferon-beta treatment in multiple sclerosis Manuel Comabella a, ⁎ , Jordi Río a , Carmen Espejo a , Mamen Ruiz de Villa b , Hammad Al-zayat a , Carlos Nos a , Florian Deisenhammer c , Sergio E. Baranzini d , Lara Nonell a , Cristina López a , Eva Julià a , Jorge R. Oksenberg d , Xavier Montalban a a Unitat de Neuroimmunologia Clínica, CEM-Cat, Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain b Departament d'Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain c Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria d Department of Neurology, School of Medicine, University of California San Francisco, USA Received 23 May 2008; accepted with revision 3 September 2008 Available online 21 October 2008 Abstract Matrix metalloproteinases (MMPs) and tissue inhibitors (TIMPs) play a key role in the pathogenesis of multiple sclerosis (MS) and have been proposed as biomarkers of response to therapy. We investigated serum levels of several MMPs and TIMPs in 43 relapsing–remitting MS (RRMS) patients undergoing interferon-beta (IFN-b) treatment and classified as responders and non-responders based on clinical criteria. Levels of MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 were determined by ELISA before treatment and after 3, 6, 12, and 24 months of therapy. Neutralizing antibodies were determined by the myxovirus A induction bioassay. Treatment with IFN-b induced changes in levels of MMP-9 and TIMP-1. In contrast to non-responders, IFN-b resulted in an early and sustained increase in TIMP-1 levels in MS patients who showed clinical response to IFN-b. The early and sustained increase in TIMP-1 levels could be a marker of the response to IFN-b during the first 2 years of treatment. © 2008 Elsevier Inc. All rights reserved. KEYWORDS Multiple sclerosis; Metalloproteinases; Interferon beta Introduction Recombinant human interferon-beta (IFN-b) is a partially effective treatment for relapsing remitting multiple sclerosis (RRMS) because of its ability to reduce relapse rate, as well as activity and burden of the disease as assessed by magnetic resonance (MR) [1–3]. Nevertheless, the cost of the drug is significant, the drug is associated with a number of side ⁎ Corresponding author. Unitat de Neuroimmunologia Clínica, CEM- Cat. Edif. EUI 2 a planta, Hospital Universitari Vall d'Hebron. Pg. Vall d'Hebron 119-129 08035 Barcelona, Spain. Fax: +34 932746084. E-mail address: mcomabel@ir.vhebron.net (M. Comabella). 1521-6616/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.clim.2008.09.010 available at www.sciencedirect.com www.elsevier.com/locate/yclim Clinical Immunology (2009) 130, 145–150