Prediction of disease severity in neuromyelitis optica by the levels of interleukin (IL)-6 produced during remission phase. (1st December 2015)

• Record Type: Journal Article
• Authors: Barros, P O; Cassano, T; Hygino, J; Ferreira, T B; Centurião, N; Kasahara, T M; Andrade, R M; Linhares, U C; Andrade, A F B; Vasconcelos, C C F; Alvarenga, R; Marignier, R; Bento, C A M
• Is Part Of: Clinical and experimental immunology. Volume 183:Number 3(2016:Mar.)
• Page Start: 480
• Page End: 489
• Publication Date: 2015-12-01
• Subjects: IL-6 -- IL-10 -- IL-21 -- IL-6R signalling -- neuromyelitis optica; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12733
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: 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.