The Ex Vivo Production of IL-6 and IL-21 by CD4+ T Cells is Directly Associated with Neurological Disability in Neuromyelitis Optica Patients

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.

Preterm cord blood CD4+ T cells exhibit increased IL-6 production in chorioamnionitis and decreased CD4+ T cells in bronchopulmonary dysplasia

“…For instance, IL-6 production by CD4 + T cells has been associated with bone loss in a gingivitis model in mice [28]. Additionally, patients with the autoimmune disorder neuromyelitis optica, which targets optic neurons, also exhibit IL-6 production by CD4 + T cells [29]. This is also true for patients with relapsing/remitting multiple sclerosis [27].…”

“…It transiently decreased the Tregs and increased IL-17A production in lymphoid organs [24-26]. In other chronic inflammatory states, increased IL-6 production by CD4 + non-regulatory T cells (non-Tregs) has been reported [27-29]. It is possible that the pro-inflammatory state observed in CA infants results from or causes reduced CD4 + cell numbers and/or function that in turn contribute to self-injurious inflammation in these infants.…”

Treatment of neuromyelitis optica: state-of-the-art and emerging therapies

“…Corticosteroids have a myriad of anti-inflammatory and immunosuppressive effects, including reduction in circulating lymphocytes and monocytes; decreased expression of cell adhesion molecules and metalloproteinases; and altered transcription of proinflammatory cytokines. 52 Interestingly, T-helper cell 17 (T H 17) cytokines such as IL-17A, IL-6 and IL-23p19, 53,54 the levels of which are elevated during NMO exacerbations, are downregulated by corticosteroids. 55 In addition to a direct role in removing pathogenic AQP4-IgG, plasma exchange could similarly reduce levels of proinflammatory cytokines, alter the numbers of T cells and B cells, and modify T H -cell phenotypes.…”

IL-21 and Related Diseases

“…With PHA stimulation, PBMCs from NMO patients produced more IL-21 than healthy individuals. The release of IL-6 as well as IL-21 by polyclonal activated CD4 + T cells was directly correlated to neurological disability, which may be the reason for NMO patients' being more refractory to corticoid treatment [68].…”