Teriflunomide and monomethylfumarate target HIV-induced neuroinflammation and neurotoxicity

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. © 2017 the author(s).