Simvastatin exerts its anti-inflammatory effect in hypercholesterolaemic patients by decreasing the serum levels of monocyte chemoattractant protein-1

Rallidis, Lοukianos S.; Hamodraka, E.; Fountoulaki, Katerina; Moustogiannis, Georgios; Zolindaki, Maria; Kremastinos, Dimitrios Th.

doi:10.1016/j.ijcard.2006.12.059

Cited by 14 publications

(11 citation statements)

References 10 publications

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“…5), which is consistent with other reports (Pasceri, Cheng et al 2001; Han, Ryu et al 2005; Wang, Zou et al 2006; Rallidis, Hamodraka et al 2008). MCP-1 is believed to be a principal driver of monocyte trafficking into the CNS (Eugenin, Osiecki et al 2006; Dhillon, Williams et al 2008).…”

Section: Discussionsupporting

confidence: 93%

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

2016

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HIV-1 associated neurocognitive disorders (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 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 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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Section: Discussionsupporting

confidence: 93%

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

2016

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“…Simvastatin can significantly decrease the expression of the pro-inflammatory cytokine MCP-1 in human umbilical vein endothelial cells and in PBMCs isolated from hypercholesterolemic patients and healthy normolipemic donors, as well as in the serum of hypercholesterolemic patients (Rezaie-Majd et al, 2002;Rallidis et al, 2008;Montecucco et al, 2009). Simvastatin has been reported to increase the serum level of the anti-inflammatory cytokine IL-10 in unstable angina patients (Li et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Effects of Curcuma comosa on the expression of atherosclerosis-related cytokine genes in rabbits fed a high-cholesterol diet

Charoenwanthanang

Lawanprasert

Phivthong-ngam

et al. 2011

Journal of Ethnopharmacology

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“…31,32 The reduction in MCP-1 observed on day 5 ( Figure 2C ) is characteristic of statin treatment. [33][34][35][36] Given the reported association of increased TNF production with severity of neurologic illness in cerebral malaria in humans and mice, [37][38][39][40] it is important to note that statin treatment failed to decrease TNF production in vivo ( Figure 2D ).…”

Section: Discussionmentioning

confidence: 99%

Statins Fail to Improve Outcome in Experimental Cerebral Malaria and Potentiate Toll-Like Receptor-Mediated Cytokine Production by Murine Macrophages

Helmers

Gowda²,

Kain

et al. 2009

The American Journal of Tropical Medicine and Hygiene

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Abstract. Cerebral malaria is responsible for a large proportion of the estimated one million deaths caused by Plasmodium falciparum malaria annually. This disease is associated with excessive pro-inflammatory cytokine production resulting from dysregulated host responses to infection. On the basis of reports indicating potent activity against host-mediated inflammatory disorders such as sepsis, we examined the activity of statins (3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors) on malaria-associated inflammation in vivo and in vitro . Simvastatin failed to improve survival or alter parasitemia in C57BL/6 mice infected with Plasmodium berghei ANKA, an experimental model of cerebral malaria. In vitro statin treatment potentiated production of tumor necrosis factor and interleukin-6 by murine peritoneal macrophages in response to P. falciparum glycosylphosphatidyl inositol, a Toll-like receptor 2 (TLR2) ligand. Statin treatment also potentiated pro-inflammatory cytokine production stimulated by a panel of TLR2 and TLR4 ligands. Our results indicate that statins fail to confer protection in experimental cerebral malaria and potentiate TLR-mediated proinflammatory cytokine production by primary murine macrophages.

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Simvastatin exerts its anti-inflammatory effect in hypercholesterolaemic patients by decreasing the serum levels of monocyte chemoattractant protein-1

Cited by 14 publications

References 10 publications

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

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

Effects of Curcuma comosa on the expression of atherosclerosis-related cytokine genes in rabbits fed a high-cholesterol diet

Statins Fail to Improve Outcome in Experimental Cerebral Malaria and Potentiate Toll-Like Receptor-Mediated Cytokine Production by Murine Macrophages

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