NDLI: Statin modulation of monocyte phenotype and function: implications for HIV-1-associated neurocognitive disorders

Content Provider	Springer Nature Link
Author	Yadav, Anjana Betts, Michael R. Collman, Ronald G.
Copyright Year	2016
Abstract	HIV-1-associated neurocognitive disorder (HAND) remains a persistent problem despite antiretroviral therapy (ART), largely a result of continued inflammation in the periphery and the brain and neurotoxin release from activated myeloid cells in the CNS. CD14+CD16+ inflammatory monocytes, expanded in HIV infection, play a central role in the pathogenesis of HAND and have parallels with monocyte-dependent inflammatory mechanisms in atherosclerosis. Statins, through their HMG-CoA reductase inhibitor activity, have pleiotropic immunomodulatory properties that contribute to their benefit in atherosclerosis beyond lipid lowering. Here, we investigated whether statins would modulate the monocyte phenotype and function associated with HIV-1 neuropathogenesis. Treatment ex vivo with simvastatin and atorvastatin reduced the proportion of CD16+ monocytes in peripheral blood mononuclear cells, as well as in purified monocytes, especially CD14++CD16+ “intermediate” monocytes most closely associated with neurocognitive disease. Statin treatment also markedly reduced expression of CD163, which is also linked to HAND pathogenesis. Finally, simvastatin inhibited production of monocyte chemoattractant protein-1 (MCP-1) and other inflammatory cytokines following LPS stimulation and reduced monocyte chemotaxis in response to MCP-1, a major driver of myeloid cell accumulation in the CNS in HAND. Together, these findings suggest that statin drugs may be useful to prevent or reduce HAND in HIV-1-infected subjects on ART with persistent monocyte activation and inflammation.
Starting Page	584
Ending Page	596
Page Count	13
File Format	PDF
ISSN	13550284
Journal	Journal of NeuroVirology
Volume Number	22
Issue Number	5
e-ISSN	15382443
Language	English
Publisher	Springer International Publishing
Publisher Date	2016-03-28
Publisher Place	Cham, Switzerland
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Monocyte NeuroAIDS HAND Statin Neurosciences Virology Infectious Diseases Immunology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Virology Neurology (clinical) Cellular and Molecular Neuroscience

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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