Mehanizmi djelovanja interferona beta u liječenju pacijenata s multiplom sklerozom [Immunomodulatory mechanisms of interferon beta in patients with multiple sclerosis]

Marković-Pleše, Silva (2011) Mehanizmi djelovanja interferona beta u liječenju pacijenata s multiplom sklerozom [Immunomodulatory mechanisms of interferon beta in patients with multiple sclerosis]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

IFNβ has been used over the past decade as an effective first-line therapy for RR MS, but its mechanisms of action are not yet fully understood. Our in-vitro study has characterizef the immunoregulatory effects of IFNβ on the production of Th17 regulatory cytokines by dendritic cells and by B-lymphocytes. Our results have demonstrated that IFNβ inhibits secretion of IL-1β, IL-23 and TGF-β, which promote Th17 cell differentiation, and induces IL-27, IL-12p35 and IL-10, which suppress it. Our results imply that the administration of high doses of recombinant IFNβ, which has a proven therapeutic effect, can increase the natural IFNβ-mediated control of autoimmune responses. Our results have identified biomarkers of Th17 cell activity that correlate with clinical disease activity and may serve as a measure of the effectiveness of IFNβ therapy.

Abstract in Croatian

IFNβ je korišten tijekom proteklog desetljeća kao učinkovita prva linija terapije protiv RR MS, no njegovi mehanizmi djelovanja još nisu u potpunosti razjašnjeni. Naša in-vitro studija je karakterizirala imunoregulatorne efekte IFNβ-a na proizvodnju Th17 regulatornih citokina od strane dendritičkih stanica i B-limfocita. IFNβ inhibira IL-1β, IL-23 i TGF-β koji potiču Th17 staničnu diferencijaciju, te inducira IL-27, IL-12p35 i IL-10, koje se suprimiraju. Naši rezultati impliciraju da administracija visokih doza rekombinantnog IFNβ, koji ima dokazani terapeutski učinak, može pojačati prirodnu IFNβ-posredovanu kontrolu autoimunog odgovora. Navedeni rezultati su identificirali biomarkere Th17 stanične aktivnosti koji su povezani s kliničkom aktivnošću bolesti, te mogu poslužiti kao mjera učinkovitosti terapije IFNβ-om.

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