Teriflunomide and monomethylfumarate target HIV-induced neuroinflammation and neurotoxicity.

Ambrosius, Björn; Faissner, Simon; Guse, Kirsten; von Lehe, Marec; Grunwald, Thomas; Gold, Ralf; Grewe, Bastian; Chan, Andrew (2017). Teriflunomide and monomethylfumarate target HIV-induced neuroinflammation and neurotoxicity. Journal of neuroinflammation, 14(1), p. 51. BioMed Central 10.1186/s12974-017-0829-2

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Sahli Building > Forschungsgruppe Neurologie

UniBE Contributor:

Guse, Kirsten and Chan, Andrew

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1742-2094

Publisher:

BioMed Central

Language:

English

Submitter:

Stefanie Hetzenecker

Date Deposited:

21 Nov 2017 15:10

Last Modified:

26 Nov 2017 02:19

Publisher DOI:

10.1186/s12974-017-0829-2

PubMed ID:

28284222

Uncontrolled Keywords:

Dimethyl fumarate Glial activation HAND HIV-associated neurocognitive disorder Leflunomide Microglia Neuroinflammation

BORIS DOI:

10.7892/boris.106348

URI:

https://boris.unibe.ch/id/eprint/106348

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