Hydroxychloroquine reduces microglial activity and attenuates experimental autoimmune encephalomyelitis

Marcus W. Koch, Rana K Zabad, Fabrizio Giuliani, Walter Hader, Ray Lewkonia, Luanne Metz, V. Wee Yong

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)131-137
Number of pages7
JournalJournal of the neurological sciences
Volume358
Issue number1-2
DOIs
StatePublished - Nov 15 2015

Fingerprint

Hydroxychloroquine
Autoimmune Experimental Encephalomyelitis
Microglia
Spinal Cord
Demyelinating Diseases
Lipopolysaccharides
Anti-Inflammatory Agents
Macrophages
Cytokines
Interleukin-1 Receptors
Antimalarials
Interleukin-12
Interleukin-10
Interleukin-6
Histology

Keywords

  • EAE
  • Hydroxychloroquine
  • Macrophage
  • Microglia
  • Multiple sclerosis

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Hydroxychloroquine reduces microglial activity and attenuates experimental autoimmune encephalomyelitis. / Koch, Marcus W.; Zabad, Rana K; Giuliani, Fabrizio; Hader, Walter; Lewkonia, Ray; Metz, Luanne; Wee Yong, V.

In: Journal of the neurological sciences, Vol. 358, No. 1-2, 15.11.2015, p. 131-137.

Research output: Contribution to journalArticle

Koch, Marcus W. ; Zabad, Rana K ; Giuliani, Fabrizio ; Hader, Walter ; Lewkonia, Ray ; Metz, Luanne ; Wee Yong, V. / Hydroxychloroquine reduces microglial activity and attenuates experimental autoimmune encephalomyelitis. In: Journal of the neurological sciences. 2015 ; Vol. 358, No. 1-2. pp. 131-137.
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