Evaluation of Th17-related cytokines and receptors in multiple sclerosis patients under interferon beta-1 therapy Gunes Esendagli a , Asli Tuncer Kurne b, ⁎, Guliz Sayat b , Ahmet Kasim Kilic b , Dicle Guc a , Rana Karabudak b a Department of Basic Oncology, Institute of Oncology, Hacettepe University, Ankara, Turkey b Hacettepe University Faculty of Medicine, Department of Neurology, Ankara, Turkey abstract article info Article history: Received 30 July 2012 Received in revised form 29 August 2012 Accepted 16 October 2012 Keywords: Multiple sclerosis IL-17 IL-23 IL-26 IL-17R IL-23R Th17-related cytokines (IL-17, IL-23, and IL-26) and receptors (IL-17R and IL-23R) were evaluated in MS patients under immunomodulatory IFN-β1 therapy during a 2 year follow-up. Before the initiation of treat- ment, no significant difference was found in cytokine or receptor expression between controls and MS patients. Of the three cytokines evaluated, IL-26 was the highest in the patients' sera. The amount of IL-17 and CD13 + IL-17R + cells was steadily decreased whereas IL-23 and IL-26 levels were gradually increased with IFN-β1 therapy. The patients in progressive phase had very high levels of IL-17. Th17-associated param- eters should be considered in the immunomodulatory IFN-β1 therapy of MS. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Multiple sclerosis (MS), the inflammatory demyelinating disease of the central nervous system (CNS) has a certain autoimmune back- ground. T helper cells play a critical role in the disease onset and pro- gression. In MS, neuroinflammation is largely mediated by IL-17 and IFN-γ cytokines. Increased amount of T helper 17 (Th17) cells, especially localized in the active areas of brain lesions, has been asso- ciated with disease severity in MS patients (Matusevicius et al., 1999; Lock et al., 2002; Tzartos et al., 2008; Montes et al., 2009). As also demonstrated in experimental allergic encephalomyelitis (EAE) models, Th17 cells migrate more efficiently than Th1 cells and display cytotoxic activity against neurons (Kebir et al., 2007). In addition, the frequency of Th17 cells is significantly higher in the cerebrospinal fluid of relapsing remitting MS (RRMS) patients during relapse, compared to those of in remission or with other non-inflammatory neurological diseases (Brucklacher-Waldert et al., 2009). Differentiation of naïve CD4 + T cells into Th17 subset is maintained by IL-21 and IL-23 cytokines (Dong, 2008). IL-23 is pro- duced by tissue-resident antigen presenting cells, i.e. dendritic cells and macrophages, loaded with self-antigens that can facilitate the ac- tivation of autoreactive Th17 cells (Akdis et al., 2011). Hence, Th17 cells are generally found in the inflamed areas and can be identified with IL-23R expression. IL-17 and IL-26 are characteristic cytokines expressed by Th17 cells (Dong, 2008). The cognate interaction be- tween IL-17 and its receptor which is broadly expressed on a variety of cells including cells of myeloid origin and epithelial cells, leads to exacerbation of immune responses via upregulation of proinflammatory cytokines, chemokines and proteases (Gaffen, 2009; Akdis et al., 2011). The role of IL-26 has not been clearly elucidated since any orthologous genes are found in murine species. Nevertheless, as a member of IL-10 immunoregulatory cytokine family, its expression has been associated with the protection from autoimmune disorders such as MS and rheu- matoid arthritis (Akdis et al., 2011). Interferon-β (IFN-β) has been shown to have therapeutic benefit by reducing relapses in MS (Neurology, The IFNβ Multiple Sclerosis Study Group, 1993). The immunomodulatory effects of IFN-β have been attributed to inhibition of T cell activation and proliferation, apoptosis of autoreactive T cells, induction of regulatory T cells, and to inhibition of leukocyte migration across the blood–brain barrier (Dhib-Jalbut and Marks, 2010). Recently, the immunoregulatory effects of IFN-β1a on Th17 cells including modulation of viability, cytokine expression, and differentiation have been pointed out (Zhang and Markovic-Plese, 2010; Chen et al., 2012; Kurtuncu et al., 2012; Wen et al., 2012). In this study, the long-term effects of immunomodulatory IFN-β1a therapy on Th17-related cytokines and their specific receptors, namely IL-17 and IL-17R, IL-23 and Il-23R, and IL-26 were assessed in RRMS patients. Besides, these parameters were also evaluated in rapidly pro- gressive patients. Journal of Neuroimmunology 255 (2013) 81–84 ⁎ Corresponding author at: Hacettepe University Faculty of Medicine, Department of Neurology, 06100, Ankara, Turkey. Tel.: +90 3123051809; fax: +90 312 3051983. E-mail address: akurne@hacettepe.edu.tr (A.T. Kurne). 0165-5728/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jneuroim.2012.10.009 Contents lists available at SciVerse ScienceDirect Journal of Neuroimmunology journal homepage: www.elsevier.com/locate/jneuroim