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

Abstract

SummaryT 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 1 T cell behaviour. High production of IL-6, IL-17 and IL-21 by CD4 1 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 1 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.

Effects of neuromyelitis optica–IgG at the blood–brain barrier in vitro

“…Certainly, peripheral sources of IL-6 are important for disease pathogenesis as revealed by the therapeutic trials using tocilizumab 25,33 and the potential prediction of disease severity by measuring plasma IL-6 levels. 34 Of note, IL-6 receptor blockade has been reported as a promising strategy to reduce NMO attack frequency. 25,33,35,36 The results we present suggest a potential amelioration of attack severity as well.…”

Treatment of Neuromyelitis Optica Spectrum Disorder: Acute, Preventive, and Symptomatic

“…The rationale behind testing an IL-6 receptor antagonist in NMOSD is based on the reportedly high levels of the pro-inflammatory IL-6 measured in the blood and spinal fluid of relapsing, actively inflamed NMOSD patients [45–47]. In a pilot study of seven Japanese NMOSD patients, tocilizumab added to background immunosuppressants such as azathioprione or prednisone provided additional reduction in relapse rates [48].…”

Immunopathology alters Th17 cell glucocorticoid sensitivity

“…Suppression of cytokines such as IL‐6 may sensitize Th17 cells to glucocorticoid suppression. Glucocorticoids are highly effective in suppressing IL‐6, and anti‐IL‐6R mAbs potentiate the ability of glucocorticoids to suppress Th17 cytokines . Tocilizumab, a humanized anti‐IL‐6 receptor monoclonal antibody, has outstanding efficacy against rheumatoid arthritis .…”