ORIGINAL RESEARCH The Ex Vivo Production of IL-6 and IL-21 by CD4 + T Cells is Directly Associated with Neurological Disability in Neuromyelitis Optica Patients Ulisses C. Linhares & Patrícia B. Schiavoni & Priscila O. Barros & Taissa M. Kasahara & Bruna Teixeira & Thais B. Ferreira & Regina Alvarenga & Joana Hygino & Morgana M. M. Vieira & Vera Carolina B. Bittencourt & Regis M. Andrade & Arnaldo F. Andrade & Cleonice A. M. Bento Received: 30 November 2011 / Accepted: 15 February 2012 / Published online: 5 September 2012 # Springer Science+Business Media, LLC 2012 Abstract Neuromyelitis optica (NMO), also known as Devic’ s disease, is an autoimmune, inflammatory disorder of the central nervous system (CNS) in which the immune sys- tem attacks myelin of the neurons located at the optic nerves and spinal cord, thus producing a simultaneous or sequential optic neuritis and myelitis. The objective of this study was evaluated the background T-cell function of patients suffering from neuromyelitis optica (NMO), an autoimmune disorder of the central nervous system. In our study, the in vitro T cell proliferation and the production of Th1 cytokines were sig- nificantly lower in cell cultures from NMO patients, as com- pared with healthy individuals. In contrast, a dominant Th17- like phenotype, associate with higher IL-23 and IL-6 produc- tion by LPS-activated monocytes, was observed among NMO patients. The release of IL-21 and IL-6 by polyclonaly acti- vated CD4 + T cells was directly correlated to neurological disability. In addition, the in vitro release of IL-21, IL-6 and IL-17 was significantly more resistant to glucocorticoid inhi- bition in NMO patients. In conclusion, the results indicate dominate Th17-related response in NMO patients that was directly proportional to neurological disability. Furthermore, our results can help to explain why NMO patients trend to be more refractory to corticoid treatment. Keywords Neuromyelitis optica . cytokines . Th17 . IL-21 . glucocorticoid Introduction Neuromyelitis optica (NMO), also known as Devic’ s dis- ease, is an autoimmune, inflammatory disorder of the central nervous system (CNS) in which the immune system attacks myelin of the neurons located at the optic nerves and spinal cord, thus producing a simultaneous or sequential optic neuritis and myelitis [1, 2]. In the past, neurologists consid- ered NMO as a particular subtype of MS. Nevertheless, several sources of evidence including not only differences in pathology and neuroimaging [3, 4], but also response to some immunotherapies [5, 6] and the recent discovery of anti-aquaporin-4 (AQP4) antibody in the serum of NMO This work was supported by Fundação Carlos Chagas Filho de amparo à pesquisa do estado do Rio de Janeiro (FAPERJ) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). U. C. Linhares : P. B. Schiavoni : R. Alvarenga Postgraduate Program in Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil P. O. Barros : T. M. Kasahara : B. Teixeira : T. B. Ferreira : J. Hygino : M. M. M. Vieira : V. C. B. Bittencourt : C. A. M. Bento (*) Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Frei Caneca 94, 20.261-040, Rio de Janeiro, RJ, Brazil e-mail: cbento@unirio.br R. M. Andrade Department of General Medicine/Federal University of the State of Rio de Janeiro, University of State of Rio de Janeiro, Rio de Janeiro, Brazil A. F. Andrade Department of Microbiology, Immunology and Parasitology, University of State of Rio de Janeiro, Rio de Janeiro, Brazil J Clin Immunol (2013) 33:179–189 DOI 10.1007/s10875-012-9780-2