Interleukin-6 in neuromyelitis optica spectrum disorder pathophysiology

Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder that preferentially affects the spinal cord and optic nerve. Most patients with NMOSD experience severe relapses that lead to permanent neurologic disability; therefore, limiting frequency and severity of these attacks is the primary goal of disease management. Currently, patients are treated with immunosuppressants. Interleukin-6 (IL-6) is a pleiotropic cytokine that is significantly elevated in the serum and the CSF of patients with NMOSD. IL-6 may have multiple roles in NMOSD pathophysiology by promoting plasmablast survival, stimulating the production of antibodies against aquaporin-4, disrupting blood-brain barrier integrity and functionality, and enhancing proinflammatory T-lymphocyte differentiation and activation. Case series have shown decreased relapse rates following IL-6 receptor (IL-6R) blockade in patients with NMOSD, and 2 recent phase 3 randomized controlled trials confirmed that IL-6R inhibition reduces the risk of relapses in NMOSD. As such, inhibition of IL-6 activity represents a promising emerging therapy for the management of NMOSD manifestations. In this review, we summarize the role of IL-6 in the context of NMOSD.

The possible role of Interleukin-6 as a regulator of insulin sensitivity in patients with neuromyelitis optica spectrum disorder

“…Within the immune system, IL-6 is secreted by immunocytes and activated astrocytes [ 40 ]. It plays a key part in the adaptive immune response in NMOSD pathogenesis [ 41 – 43 ] by stimulating immunoglobulin (Ig) synthesis in activated B cells and Th17 cells or cytotoxic T cells development [ 42 , 44 – 47 ]. Within the metabolic pathways, it has impairing effects on the insulin signaling which could result in IR and related diseases [ 39 , 48 ] via NF-kB signaling.…”

The diagnostic dilemma of NMOSD/anti-MOG Antibody and Pseudotumor cerebri co-existence in a patient with recent COVID-19 infection.

“…Recent evidence has linked interleukin-6 (IL-6) to disease activity in NMOSD by mechanism of promoting survival of plasmablasts, stimulation of AQP4-IgG secretion, altering integrity and functionality of BBB and increasing differentiation and activation of pro-inflammatory T-lymphocytes. In patients with NMOSD, IL-6 levels in the serum and CSF are significantly increased [25] . Interlinking this to elevated IL-6 levels in SARS-CoV-2 infection may explain the underlying pathophysiology for occurrence of NMOSD in cases of recent COVID-19 infection.…”

The Possible Role of Interleukin-6 as a Regulator of Insulin Sensitivity in Patients With Neuromyelitis Optica Spectrum Disorder

“…In the course of NMOSD, IL-6 as a humoral immune system factor plays an essential role in NMOSD pathogenesis [29][30][31]. Interleukin-6 supports plasma cell differentiation and survival and has a potential role in the induction of plasmablasts and/or plasma cells that produce autoantibodies against AQP4 and other relevant antigens [32,33].…”