OBJECTIVES: There is convergent evidence for an important role of interleukin-16 (IL-16) in the pathogenesis of multiple sclerosis (MS). IL-16 serves as a chemoattractant for different immune cells that are involved in developing lesions. Here, we compared IL-16 levels of MS patients and controls and addressed the long-term effect of IFN-β, the most common immunomodulatory MS therapy, on IL-16 serum levels in MS patients over 2 years. Beyond this, we analysed the expression of IL-16 in two CD4(+) T-cell subsets, Th1 and Th17 cells, which are important autoimmune mediators and affected by IFN-β treatment, derived from myelin-specific T-cell transgenic mice. MATERIALS AND METHODS: IL-16 serum levels of 17 controls and of 16 MS patients before therapy and at months 1, 2, 3, 6, 9, 12 and 24 during IFN-β1a therapy were determined by ELISA. MRI was performed before therapy, at months 12 and 24. IL-16 expression of in vitro differentiated murine myelin oligodendrocyte glycoprotein (MOG)-specific Th1 and Th17 cells was quantified by real-time PCR. RESULTS: Before therapy, MS patients showed significantly elevated IL-16 levels compared with controls irrespective of disease activity determined by MRI. Therapy with IFN-β1a led to a significant linear decrease in IL-16 serum levels beginning after 2 months. MOG-specific Th17 cells expressed more IL-16 than Th1 cells. CONCLUSIONS: Reduction in increased IL-16 levels may be of relevance for the therapeutic effect of IFN-β1a in MS. Easily accessible IL-16 serum levels hold a potential as biomarker of treatment efficacy in MS.
OBJECTIVES: There is convergent evidence for an important role of interleukin-16 (IL-16) in the pathogenesis of multiple sclerosis (MS). IL-16 serves as a chemoattractant for different immune cells that are involved in developing lesions. Here, we compared IL-16 levels of MSpatients and controls and addressed the long-term effect of IFN-β, the most common immunomodulatory MS therapy, on IL-16 serum levels in MSpatients over 2 years. Beyond this, we analysed the expression of IL-16 in two CD4(+) T-cell subsets, Th1 and Th17 cells, which are important autoimmune mediators and affected by IFN-β treatment, derived from myelin-specific T-cell transgenic mice. MATERIALS AND METHODS:IL-16 serum levels of 17 controls and of 16 MSpatients before therapy and at months 1, 2, 3, 6, 9, 12 and 24 during IFN-β1a therapy were determined by ELISA. MRI was performed before therapy, at months 12 and 24. IL-16 expression of in vitro differentiated murinemyelin oligodendrocyte glycoprotein (MOG)-specific Th1 and Th17 cells was quantified by real-time PCR. RESULTS: Before therapy, MSpatients showed significantly elevated IL-16 levels compared with controls irrespective of disease activity determined by MRI. Therapy with IFN-β1a led to a significant linear decrease in IL-16 serum levels beginning after 2 months. MOG-specific Th17 cells expressed more IL-16 than Th1 cells. CONCLUSIONS: Reduction in increased IL-16 levels may be of relevance for the therapeutic effect of IFN-β1a in MS. Easily accessible IL-16 serum levels hold a potential as biomarker of treatment efficacy in MS.
Authors: Ari V Ahola-Olli; Peter Würtz; Aki S Havulinna; Kristiina Aalto; Niina Pitkänen; Terho Lehtimäki; Mika Kähönen; Leo-Pekka Lyytikäinen; Emma Raitoharju; Ilkka Seppälä; Antti-Pekka Sarin; Samuli Ripatti; Aarne Palotie; Markus Perola; Jorma S Viikari; Sirpa Jalkanen; Mikael Maksimow; Veikko Salomaa; Marko Salmi; Johannes Kettunen; Olli T Raitakari Journal: Am J Hum Genet Date: 2016-12-15 Impact factor: 11.025
Authors: D L Sampson; B A Fox; T D Yager; S Bhide; S Cermelli; L C McHugh; T A Seldon; R A Brandon; E Sullivan; J J Zimmerman; M Noursadeghi; R B Brandon Journal: Sci Rep Date: 2017-06-06 Impact factor: 4.379