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Endogenous interleukin‐6 amplifies interleukin‐17 production and corticoid‐resistance in peripheral T cells from patients with multiple sclerosis
Author(s) -
Ferreira Thais B.,
Hygino Joana,
Barros Priscila O.,
Teixeira Bruna,
Kasahara Taissa M.,
Linhares Ulisses C.,
Lopes Lana Márcia F.,
Vasconcelos Claudia Cristina F.,
Alvarenga Regina,
Wing Ana Cristina,
Andrade Regis M.,
Andrade Arnaldo F. B.,
Bento Cleonice A. M.
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12334
Subject(s) - cytokine , t cell , immunology , cd8 , interleukin 2 , interleukin , interleukin 17 , biology , immune system
Summary 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 ‐6 R ) 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 ‐6 R signalling by anti‐ IL ‐6 R monoclonal antibody reduced IL‐17 production and elevated IL‐10 release by activated CD 4 + T cells, but it did not alter the production of these cytokines by activated CD 8 + T cells. Blockade of IL ‐6 R 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 CD 4 + and, mainly, CD 8 + T cells from patients with MS were less sensitive to hydrocortisone inhibition than control group. Interestingly, IL ‐6 R 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.