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Hydroxychloroquine reduces microglial activity and attenuates experimental autoimmune encephalomyelitis.

Abstract：

BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSION:HCQ treatment reduces the activation of human microglia in vitro, delays the onset of EAE, and decreases the representation of activated macrophages/microglia and demyelination in the spinal cord of treated mice. HCQ is a plausible candidate for further clinical studies in MS.

journal_name

J Neurol Sci

journal_title

Journal of the neurological sciences

authors

Koch MW,Zabad R,Giuliani F,Hader W Jr,Lewkonia R,Metz L,Wee Yong V

doi

10.1016/j.jns.2015.08.1525

subject

Has Abstract

pub_date

2015-11-15 00:00:00

pages

131-7

issue

1-2

eissn

0022-510X

issn

1878-5883

pii

S0022-510X(15)02021-3

journal_volume

358

pub_type

杂志文章

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