title: Endogenous interleukin-6 amplifies interleukin-17 production and corticoid-resistance in peripheral T cells from patients with multiple sclerosis.
abstract: Interleukin-6 (IL-6) has been implicated in the induction of pathogenic IL-17-producing T cells in autoimmune diseases, and studies evaluating the role of this cytokine in T-cell function in patients with multiple sclerosis (MS) are lacking. Our objective was to evaluate the role of IL-6 receptor (IL-6R) signalling on in vitro functional status of T cells from patients with relapsing-remitting MS during clinical remission. Our results demonstrated that, even during the remission phase, activated T cells from patients produce higher levels of IL-17, and this cytokine was positively correlated with disease severity, as determined by Expanded Disability Status Scale score. In the MS group, the blockade of IL-6R signalling by anti-IL-6R monoclonal antibody reduced IL-17 production and elevated IL-10 release by activated CD4(+) T cells, but it did not alter the production of these cytokines by activated CD8(+) T cells. Blockade of IL-6R signalling also reduced the ability of monocytes to up-regulate T helper type 17 phenotype in patients with MS. Finally, both cell proliferation and IL-17 release by CD4(+) and, mainly, CD8(+) T cells from patients with MS were less sensitive to hydrocortisone inhibition than control group. Interestingly, IL-6R signalling blockade restored the ability of hydrocortisone to inhibit both T-cell proliferation and IL-17 production. Collectively, these results suggest that IL-6 might be involved in MS pathogenesis by enhancing IL-17 production and reducing corticoid inhibitory effects on activated T cells.
authors.affiliation: Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Thais B
authors.initials: TB
authors.lastname: Ferreira
authors.forename: Joana
authors.initials: J
authors.lastname: Hygino
authors.forename: Priscila O
authors.initials: PO
authors.lastname: Barros
authors.forename: Bruna
authors.initials: B
authors.lastname: Teixeira
authors.forename: Taissa M
authors.initials: TM
authors.lastname: Kasahara
authors.forename: Ulisses C
authors.initials: UC
authors.lastname: Linhares
authors.forename: Lana Márcia F
authors.initials: LM
authors.lastname: Lopes
authors.forename: Claudia Cristina F
authors.initials: CC
authors.lastname: Vasconcelos
authors.forename: Regina
authors.initials: R
authors.lastname: Alvarenga
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Wing
authors.forename: Regis M
authors.initials: RM
authors.lastname: Andrade
authors.forename: Arnaldo F B
authors.initials: AF
authors.lastname: Andrade
authors.forename: Cleonice A M
authors.initials: CA
authors.lastname: Bento
mesh_terms: D000305:Adrenal Cortex Hormones / Q000378:metabolism / Q000494:pharmacology; D000328:Adult; D016207:Cytokines / Q000096:biosynthesis; D004351:Drug Resistance; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D016207:Cytokines; D020381:Interleukin-17; D015850:Interleukin-6; D019947:Receptors, Interleukin-6
keywords: cytokines; interleukin-10; interleukin-17; interleukin-6; multiple sclerosis