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Cited by 31HIV Research and TreatmentHIV-related health complications and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

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

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Yadav, Anjana, Betts, Michael R., Collman, Ronald G.·2016·Journal of NeuroVirology
DOI 10.1007/s13365-016-0433-8PMC PMC5040617
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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.

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  • A combination of atorvastatin and SIM decreases proportion of CD16+ monocytes in PBMC cells, which is relevant to HAND since migration of CD16+ cells into CNS accelerates HAND.

    “A combination of atorvastatin and SIM decreases the proportion of CD16+ monocytes in PBMC cells, which is relevant to HAND since the migration of CD16+ cells into the CNS accelerate HAND [80, 81].”

    From HIV-TAT dysregulates microglial lipid metabolism through SREBP2/miR-124 axis: Implication of lipid droplet accumulation microglia in NeuroHIV (2025) · cites this paper as [80]

    The Results and Discussion (page not provided) report that simvastatin and atorvastatin each reduced the proportion of CD16+ monocytes in PBMC cultures and link these cells’ migration into the CNS to HAND pathogenesis. The Methods specify treatment with simvastatin or atorvastatin, not a combination of the two, so the claimed effect of combined treatment is unsupported. (LLM, conf=0.88)

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Cited by

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Authors
Yadav, A., Betts, M. R., & Collman, R. G.
Affiliations
University of Pennsylvania (US)
Corresponding author
Collman, Ronald G.
ORCID
Venue
Journal of NeuroVirology
Publisher
Springer Science and Business Media LLC
Published
2016-03-28
Volume
22
Issue
5
Pages
584-596
ISSN
  • 1355-0284 (ISSN-L)
  • 1538-2443
DOI
10.1007/s13365-016-0433-8
PMC
PMC5040617
OpenAlex
W2325335179
Cited by
31
References
4
Citations by year
2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 10 · 2019: 3 · 2018: 3 · 2017: 4
FWCI
2.31
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of NeuroVirology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (MH061139)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
HIV-1-associated neurocognitive disorders, statins, simvastatin, atorvastatin, CD14+CD16+ monocytes, intermediate monocytes, CD163, MCP-1, monocyte chemotaxis, HMG-CoA reductase inhibition, neuroinflammation, lipopolysaccharide-induced inflammation, HIV neuropathogenesis
MeSH terms
Atorvastatin, CD163 Antigen, Chemotaxis, Gene Expression Regulation, Humans, Lipopolysaccharides, Models, Biological, Monocytes, Phenotype, Receptors, Cell Surface, Antigens, Differentiation, Myelomonocytic, Signal Transduction, AIDS Dementia Complex, Antigens, CD, Interleukin-8, Receptors, IgG, Chemokine CCL2, Lipopolysaccharide Receptors, Simvastatin, Chemokine CCL3, GPI-Linked Proteins, Primary Cell Culture, Healthy Volunteers

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