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Open Access 01-12-2017 | Short report

Teriflunomide and monomethylfumarate target HIV-induced neuroinflammation and neurotoxicity

Authors: Björn Ambrosius, Simon Faissner, Kirsten Guse, Marec von Lehe, Thomas Grunwald, Ralf Gold, Bastian Grewe, Andrew Chan

Published in: Journal of Neuroinflammation | Issue 1/2017

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.

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Title: Teriflunomide and monomethylfumarate target HIV-induced neuroinflammation and neurotoxicity
Authors: Björn Ambrosius
Simon Faissner
Kirsten Guse
Marec von Lehe
Thomas Grunwald
Ralf Gold
Bastian Grewe
Andrew Chan
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-017-0829-2

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Teriflunomide and monomethylfumarate target HIV-induced neuroinflammation and neurotoxicity

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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