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Clin Exp Immunol. 2016 Mar;183(3):480-9. doi: 10.1111/cei.12733. Epub 2015 Dec 1.

Prediction of disease severity in neuromyelitis optica by the levels of interleukin (IL)-6 produced during remission phase.

Author information

1
Department of Microbiology and Parasitology, Federal University of the State of Rio De Janeiro.
2
Department of General Medicine, Federal University of the State of Rio De Janeiro.
3
Postgraduate Program in Neurology, Federal University of the State of Rio De Janeiro.
4
Department of Microbiology of State University of Rio De Janeiro, Rio De Janeiro, Brazil.
5
Team ONCOFLAM, Lyon's Neuroscience Research Center, Lyon, France.

Abstract

T helper type 17 (Th17) cytokines have been implicated in the pathogenesis of neuromyelitis optica (NMO). As humanized anti-interleukin (IL)-6R (tocilizumab) immunoglobulin (Ig)G has been used as disease-modifying therapy for NMO, the objective of our study was to investigate the role of endogenous IL-6 on NMO-derived CD4(+) T cell behaviour. High production of IL-6, IL-17 and IL-21 by CD4(+) T-cells was detected in NMO patients. Further, IL-21 and IL-6 levels were related directly to the level of neurological disabilities. The addition of anti-IL-6R IgG not only reduced directly the production of these cytokines, but also almost abolished the ability of activated autologous monocytes in enhancing IL-6, IL-17 and IL-21 release by CD4(+) T cells. In contrast, the production of IL-10 was amplified in those cell cultures. Further, anti-IL-6R monoclonal antibodies (mAb) also potentiated the ability of glucocorticoid in reducing Th17 cytokines. Finally, the in-vivo and in-vitro IL-6 levels were significantly higher among those patients who experienced clinical relapse during 2-year follow-up. In summary, our results suggest a deleterious role of IL-6 in NMO by favouring, at least in part, the expansion of corticoid-resistant Th17 cells.

KEYWORDS:

IL-10; IL-21; IL-6; IL-6R signalling; neuromyelitis optica

PMID:
26472479
PMCID:
PMC4750605
[Available on 2017-03-01]
DOI:
10.1111/cei.12733
[Indexed for MEDLINE]
Free PMC Article

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