Hydroxychloroquine reduces microglial activity and attenuates experimental autoimmune encephalomyelitis

Journal of the Neurological Sciences
Marcus W KochV Wee Yong

Abstract

Microglial activation is thought to be a key pathophysiological mechanism underlying disease activity in all forms of MS. Hydroxychloroquine (HCQ) is an antimalarial drug with immunomodulatory properties that is widely used in the treatment of rheumatological diseases. In this series of experiments, we explore the effect of HCQ on human microglial activation in vitro and on the development of experimental autoimmune encephalitis (EAE) in vivo. We activated human microglia with lipopolysaccharide (LPS), and measured concentrations of several pro- and anti-inflammatory cytokines in untreated and HCQ pretreated cultures. We investigated the effect of HCQ pretreatment at two doses on the development of EAE and spinal cord histology. HCQ pretreatment reduced the production of pro-inflammatory (TNF-alpha, IL-6, and IL-12) and anti-inflammatory (IL-10 and IL-1 receptor antagonist) cytokines in LPS-stimulated human microglia. HCQ pretreatment delayed the onset of EAE, and reduced the number of Iba-1 positive microglia/macrophages and signs of demyelination in the spinal cords of HCQ treated animals. HCQ treatment reduces the activation of human microglia in vitro, delays the onset of EAE, and decreases the representation of activated m...Continue Reading

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Citations

Apr 2, 2016·Mediators of Inflammation·Xueli FanTao Jin
Jun 12, 2016·Journal of Pharmacological Sciences·Yanke ChenJia Jia
Jul 18, 2016·Journal of the Neurological Sciences·Jian-Qiang LuChristopher Power
Sep 30, 2017·International Journal of Molecular Sciences·Tobias Koeniger, Stefanie Kuerten
Apr 12, 2018·Expert Opinion on Emerging Drugs·Ram Narendra NarayanOlaf Stüve
Oct 11, 2019·Therapeutic Advances in Neurological Disorders·Simon Faissner, Ralf Gold
Sep 19, 2019·Nature Reviews. Neurology·Yifei Dong, V Wee Yong
Aug 11, 2019·Nature Reviews. Drug Discovery·Simon FaissnerV Wee Yong
Nov 17, 2020·Genome Génome / Conseil National De Recherches Canada·Wenxia LuoTed M Lakowski
Jan 8, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Dennis BrownV Wee Yong
Sep 28, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·H Ghasemnejad-BerenjiM Ghasemnejad-Berenji
Aug 31, 2021·Therapeutic Advances in Neurological Disorders·Tobias BrummerStefan Bittner
Oct 1, 2021·Annals of Neurology·Marcus W KochLuanne M Metz
Nov 5, 2021·Nature Reviews. Neurology·Heather Y F Yong, V Wee Yong

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