title: Prediction of disease severity in neuromyelitis optica by the levels of interleukin (IL)-6 produced during remission phase.
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.
authors.affiliation: Department of Microbiology and Parasitology, Federal University of the State of Rio De Janeiro.
authors.forename: P O
authors.initials: PO
authors.lastname: Barros
authors.affiliation: Department of Microbiology and Parasitology, Federal University of the State of Rio De Janeiro.
authors.forename: T
authors.initials: T
authors.lastname: Cassano
authors.affiliation: Department of Microbiology and Parasitology, Federal University of the State of Rio De Janeiro.
authors.forename: J
authors.initials: J
authors.lastname: Hygino
authors.affiliation: Department of Microbiology and Parasitology, Federal University of the State of Rio De Janeiro.
authors.forename: T B
authors.initials: TB
authors.lastname: Ferreira
authors.affiliation: Department of Microbiology and Parasitology, Federal University of the State of Rio De Janeiro.
authors.forename: N
authors.initials: N
authors.lastname: Centurião
authors.affiliation: Department of Microbiology and Parasitology, Federal University of the State of Rio De Janeiro.
authors.forename: T M
authors.initials: TM
authors.lastname: Kasahara
authors.affiliation: Department of General Medicine, Federal University of the State of Rio De Janeiro.
authors.forename: R M
authors.initials: RM
authors.lastname: Andrade
authors.affiliation: Postgraduate Program in Neurology, Federal University of the State of Rio De Janeiro.
authors.forename: U C
authors.initials: UC
authors.lastname: Linhares
authors.affiliation: Department of Microbiology of State University of Rio De Janeiro, Rio De Janeiro, Brazil.
authors.forename: A F B
authors.initials: AF
authors.lastname: Andrade
authors.affiliation: Postgraduate Program in Neurology, Federal University of the State of Rio De Janeiro.
authors.forename: C C F
authors.initials: CC
authors.lastname: Vasconcelos
authors.affiliation: Postgraduate Program in Neurology, Federal University of the State of Rio De Janeiro.
authors.forename: R
authors.initials: R
authors.lastname: Alvarenga
authors.affiliation: Team ONCOFLAM, Lyon's Neuroscience Research Center, Lyon, France.
authors.forename: R
authors.initials: R
authors.lastname: Marignier
authors.affiliation: Department of Microbiology and Parasitology, Federal University of the State of Rio De Janeiro.|Postgraduate Program in Neurology, Federal University of the State of Rio De Janeiro.
authors.forename: C A M
authors.initials: CA
authors.lastname: Bento
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D016753:Interleukin-10 / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D015850:Interleukin-6 / Q000502:physiology*; D007378:Interleukins / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000188:drug therapy* / Q000276:immunology*; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D012074:Remission Induction; D012720:Severity of Illness Index; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology; D000098546:Interleukin-21
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C508609:IL10 protein, human; C508717:IL17A protein, human; C508600:IL6 protein, human; C508603:IL6R protein, human; D020381:Interleukin-17; D015850:Interleukin-6; D007378:Interleukins; D019947:Receptors, Interleukin-6; D016753:Interleukin-10; C502936:tocilizumab; D000098546:Interleukin-21; D006854:Hydrocortisone
keywords: IL-10; IL-21; IL-6; IL-6R signalling; neuromyelitis optica