Effect of short-term interferon-b treatment on cytokines in multiple sclerosis: Significant modulation of IL-17 and IL-23 Murat Kürtüncü a , Erdem Tüzün b,⇑ , Recai Türkog ˘lu c , Belgin Petek-Balcı d , Sema _ Içöz e , Münevver Pehlivan e , Ömer Biris ßik e , Canan Ulusoy b , Erkingül Shugaiv e , Güls ßen Akman-Demir f , Mefküre Eraksoy e a Department of Neurology, Acıbadem University School of Medicine, Istanbul, Turkey b Department of Neuroscience, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey c Department of Neurology, Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey d Department of Neurology, Haseki Educational and Research Center, Istanbul, Turkey e Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey f Department of Neurology, Istanbul Bilim University, School of Medicine, Istanbul, Turkey article info Article history: Received 7 December 2011 Received in revised form 10 April 2012 Accepted 8 May 2012 Available online 30 May 2012 Keywords: Multiple sclerosis Cytokine Interleukins Th17 Th1 abstract Therapeutic effect of interferon-b (IFN-b) treatment has been associated with modulation of the balance between Th1, Th17, Th2 and regulatory T (Treg) cells, whereas the impact of disease modifying drugs on Th9-immunity in multiple sclerosis (MS) has not been studied. To investigate the short-term effects of IFN-b treatment on cytokines in MS, we determined serum levels of IL-17, IL-23, IL-10, IL-4, IFN-c, IL-9 and TGF-b in relapsing remitting MS patients before and 2 months after IFN-b treatment by ELISA. MS patients showed increased IL-17, IL-23 and IL-4 levels and decreased IL-9 levels as compared to healthy controls. IFN-b treatment only reduced IL-17 and IL-23 levels, whereas the levels of other cytokines remained unchanged. IFN-b treatment appears to exert its earliest therapeutic effect on Th17-immunity. The influence of IL-9 on MS pathogenesis needs to be further studied. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction Multiple sclerosis (MS) is one of the most common diseases of the central nervous system (CNS) in young adults. Although its exact cause is still not known, a CD4+ T cell mediated CNS inflam- mation, which triggers demyelination and axonal degeneration, has been shown to play a major role in MS pathogenesis. Th1 (e.g. IFN-c, IL-12) and Th17 (e.g. IL-17) cytokines produced by spe- cific CD4+ T cell subsets and a Th17-promoting factor IL-23 mainly produced by macrophages and dendritic cells are critically in- volved in disease mechanisms [1–3]. Current MS therapies aim to redirect the Th1 and Th17 cytokine responses to the Th2 (e.g. IL-4) and regulatory T cell (Treg) (e.g. IL-10, TGF-b) profile [4–6]. Treatment of relapsing–remitting MS with interferon-b (IFN-b) reduces the frequency and severity of clinical exacerbations and the pace of disease progression [7]. While the precise mechanisms by which IFN-b show its beneficial effects on MS are not known, at least one of these mechanisms has been proposed to be the downmodulation of Th1 and Th17 cyto- kines [8,9]. Alternatively, the influence of IFN-b on Th2 and Treg cytokines is more diverse and inconsistent [10–16]. Moreover, the role of the recently discovered Th9-type immunity in MS path- ogenesis and the impact of IFN-b treatment on IL-9 levels are not known. To evaluate the short-term in vivo effects of IFN-b treatment on different T cell subtypes, we measured the levels of major Th1, Th2, Th9, Th17 and Treg cytokines and IL-23 in sera of MS patients before and 2 months after IFN-b treatment. 2. Materials and methods 2.1. Patients Sixty-three untreated patients with relapsing–remitting MS and 30 healthy controls were included. All subjects signed an informed consent that was approved by the Ethics Committee of Istanbul Faculty of Medicine of Istanbul University prior to venipuncture. All patients had definite MS according to the McDonald criteria [17] and they had no other autoimmune or infectious diseases dur- ing blood sampling. None of the untreated patients had received an 1043-4666/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.cyto.2012.05.004 ⇑ Corresponding author. Address: Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, 34390 Çapa, Istanbul, Turkey. Tel.: +90 212 4142000x32580; fax: +90 212 5334393. E-mail address: drerdem@yahoo.com (E. Tüzün). Cytokine 59 (2012) 400–402 Contents lists available at SciVerse ScienceDirect Cytokine journal homepage: www.elsevier.com/locate/issn/10434666