Teriflunomide and monomethylfumarate target HIV-induced neuroinflammation and neurotoxicity.
J Neuroinflammation
; 14(1): 51, 2017 03 11.
Article
in En
| MEDLINE
| ID: mdl-28284222
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Toluidines
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Crotonates
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Monocytes
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HIV-1
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Microglia
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Inflammation Mediators
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Fumarates
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Maleates
Limits:
Humans
Language:
En
Journal:
J Neuroinflammation
Journal subject:
NEUROLOGIA
Year:
2017
Document type:
Article
Affiliation country:
Country of publication: