Endogenous interleukin-6 amplifies interleukin-17 production and corticoid-resistance in peripheral T cells from patients with multiple sclerosis

Authors

  • Thais B. Ferreira,

    1. Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
    Search for more papers by this author
  • Joana Hygino,

    1. Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
    Search for more papers by this author
  • Priscila O. Barros,

    1. Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
    Search for more papers by this author
  • Bruna Teixeira,

    1. Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
    Search for more papers by this author
  • Taissa M. Kasahara,

    1. Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
    Search for more papers by this author
  • Ulisses C. Linhares,

    1. Department of Anatomy and Histology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
    Search for more papers by this author
  • Lana Márcia F. Lopes,

    1. Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
    Search for more papers by this author
  • Claudia Cristina F. Vasconcelos,

    1. Post-graduate Programme in Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
    Search for more papers by this author
  • Regina Alvarenga,

    1. Post-graduate Programme in Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
    Search for more papers by this author
  • Ana Cristina Wing,

    1. Post-graduate Programme in Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
    Search for more papers by this author
  • Regis M. Andrade,

    1. Department of General Medicine, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
    Search for more papers by this author
  • Arnaldo F. B. Andrade,

    1. Department of Microbiology, Immunology and Parasitology, State University of Rio de Janeiro, Rio de Janeiro, Brazil
    Search for more papers by this author
  • Cleonice A. M. Bento

    Corresponding author
    1. Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
    2. Post-graduate Programme in Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
    • Correspondence: Dr Cleonice A. M. Bento, Department of Microbiology and Parasitology, Federal University of Rio de Janeiro State, Rua Frei Caneca 94, 20.261-040, Rio de Janeiro, RJ, Brazil.

      Email: cbento@unirio.br

      Senior author: Dr Cleonice A. M. Bento.

    Search for more papers by this author

  • The first two authors contributed equally to this work.

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-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.

Ancillary