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  4. Teriflunomide and monomethylfumarate target HIV-induced neuroinflammation and neurotoxicity
 
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2017
Journal Article
Title

Teriflunomide and monomethylfumarate target HIV-induced neuroinflammation and neurotoxicity

Abstract
HIV-associated neurocognitive disorders (HAND) affect about 50% of infected patients despite combined antiretroviral therapy (cART). Ongoing compartmentalized inflammation mediated by microglia which are activated by HIV-infected monocytes has been postulated to contribute to neurotoxicity independent from viral replication. Here, we investigated effects of teriflunomide and monomethylfumarate on monocyte/microglial activation and neurotoxicity. Human monocytoid cells (U937) transduced with a minimal HIV-Vector were co-cultured with human microglial cells (HMC3). Secretion of pro-inflammatory/neurotoxic cytokines (CXCL10, CCL5, and CCL2: p < 0.001; IL-6: p < 0.01) by co-cultures was strongly increased compared to microglia in contact with HIV-particles alone. Upon treatment with teriflunomide, cytokine secretion was decreased (CXCL10, 3-fold; CCL2, 2.5-fold; IL-6, 2.2-fold; p < 0.001) and monomethylfumarate treatment led to 2.9-fold lower CXCL10 secretion (p < 0.001). Reduced toxicity of co-culture conditioned media on human fetal neurons by teriflunomide (29%, p < 0.01) and monomethylfumarate (27%, p < 0.05) indicated functional relevance. Modulation of innate immune functions by teriflunomide and monomethylfumarate may target neurotoxic inflammation in the context of HAND.
Author(s)
Ambrosius, Björn
Universität Bochum
Faissner, Simon
University of Calgary
Guse, Kirsten
Universität Bochum
Lehe, Marec von
Knappschaftskrankenhaus Bochum
Grunwald, Thomas  
Fraunhofer-Institut für Zelltherapie und Immunologie IZI  
Gold, Ralf
Universität Bochum
Grewe, Bastian
Universität Bochum
Chan, Andrew
Universität Bern
Journal
Journal of neuroinflammation  
Open Access
Link
Link
DOI
10.1186/s12974-017-0829-2
Language
English
Fraunhofer-Institut für Zelltherapie und Immunologie IZI  
Keyword(s)
  • HIV-associated neurocognitive disorder

  • HAND

  • glial activation

  • microglia

  • leflunomide

  • dimethyl fumarate

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