The ex vivo production of IL-6 and IL-21 by CD4+ T cells is directly associated with neurological disability in neuromyelitis optica patients

J Clin Immunol. 2013 Jan;33(1):179-89. doi: 10.1007/s10875-012-9780-2. Epub 2012 Sep 5.

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 system 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 significantly lower in cell cultures from NMO patients, as compared with healthy individuals. In contrast, a dominant Th17-like phenotype, associate with higher IL-23 and IL-6 production by LPS-activated monocytes, was observed among NMO patients. The release of IL-21 and IL-6 by polyclonally activated 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 inhibition in NMO patients. In conclusion, the results indicate dominant 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • Cells, Cultured
  • Female
  • Humans
  • Interleukin-21
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / metabolism
  • Interleukins / biosynthesis*
  • Interleukins / metabolism
  • Lymphocyte Activation / immunology*
  • Male
  • Middle Aged
  • Neuromyelitis Optica / immunology*
  • Neuromyelitis Optica / metabolism
  • Neuromyelitis Optica / physiopathology

Substances

  • IL6 protein, human
  • Interleukin-6
  • Interleukins
  • Interleukin-21