PMID- 27021071
OWN - NLM
STAT- MEDLINE
DCOM- 20180124
LR  - 20181202
IS  - 1538-2443 (Electronic)
IS  - 1355-0284 (Print)
IS  - 1355-0284 (Linking)
VI  - 22
IP  - 5
DP  - 2016 Oct
TI  - Statin modulation of monocyte phenotype and function: implications for 
      HIV-1-associated neurocognitive disorders.
PG  - 584-596
AB  - 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.
FAU - Yadav, Anjana
AU  - Yadav A
AD  - Department of Medicine, University of Pennsylvania Perelman School of Medicine, 
      36th and Hamilton Walk, Philadelphia, PA, 19104, USA.
FAU - Betts, Michael R
AU  - Betts MR
AD  - Department of Microbiology, University of Pennsylvania Perelman School of 
      Medicine, 36th and Hamilton Walk, Philadelphia, PA, 19104, USA.
FAU - Collman, Ronald G
AU  - Collman RG
AD  - Department of Medicine, University of Pennsylvania Perelman School of Medicine, 
      36th and Hamilton Walk, Philadelphia, PA, 19104, USA. 
      collmanr@mail.med.upenn.edu.
AD  - Department of Microbiology, University of Pennsylvania Perelman School of 
      Medicine, 36th and Hamilton Walk, Philadelphia, PA, 19104, USA. 
      collmanr@mail.med.upenn.edu.
LA  - eng
GR  - P30 AI045008/AI/NIAID NIH HHS/United States
GR  - P30 CA016520/CA/NCI NIH HHS/United States
GR  - R01 MH061139/MH/NIMH NIH HHS/United States
PT  - Journal Article
DEP - 20160328
PL  - United States
TA  - J Neurovirol
JT  - Journal of neurovirology
JID - 9508123
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (CCL2 protein, human)
RN  - 0 (CD163 antigen)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL3)
RN  - 0 (FCGR3B protein, human)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Interleukin-8)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, IgG)
RN  - A0JWA85V8F (Atorvastatin)
RN  - AGG2FN16EV (Simvastatin)
SB  - IM
MH  - AIDS Dementia Complex/genetics/immunology/pathology
MH  - Antigens, CD/genetics/immunology
MH  - Antigens, Differentiation, Myelomonocytic/genetics/immunology
MH  - Atorvastatin/*pharmacology
MH  - Chemokine CCL2/genetics/immunology/pharmacology
MH  - Chemokine CCL3/genetics/immunology
MH  - Chemotaxis
MH  - GPI-Linked Proteins/genetics/immunology
MH  - Gene Expression Regulation/*drug effects/immunology
MH  - Healthy Volunteers
MH  - Humans
MH  - Interleukin-8/genetics/immunology
MH  - Lipopolysaccharide Receptors/genetics/immunology
MH  - Lipopolysaccharides/antagonists & inhibitors/pharmacology
MH  - Models, Biological
MH  - Monocytes/cytology/*drug effects/immunology
MH  - Phenotype
MH  - Primary Cell Culture
MH  - Receptors, Cell Surface/genetics/immunology
MH  - Receptors, IgG/genetics/immunology
MH  - Signal Transduction
MH  - Simvastatin/*pharmacology
PMC - PMC5040617
MID - NIHMS773288
OTO - NOTNLM
OT  - HAND
OT  - Monocyte
OT  - NeuroAIDS
OT  - Statin
COIS- The authors A. Yadav, M.R. Betts and R.G. Collman declare that they have no 
      conflict of interest.
EDAT- 2016/03/30 06:00
MHDA- 2018/01/25 06:00
PMCR- 2017/10/01
CRDT- 2016/03/30 06:00
PHST- 2015/09/24 00:00 [received]
PHST- 2016/02/19 00:00 [accepted]
PHST- 2016/02/08 00:00 [revised]
PHST- 2016/03/30 06:00 [pubmed]
PHST- 2018/01/25 06:00 [medline]
PHST- 2016/03/30 06:00 [entrez]
PHST- 2017/10/01 00:00 [pmc-release]
AID - 10.1007/s13365-016-0433-8 [pii]
AID - 10.1007/s13365-016-0433-8 [doi]
PST - ppublish
SO  - J Neurovirol. 2016 Oct;22(5):584-596. doi: 10.1007/s13365-016-0433-8. Epub 2016 
      Mar 28.