Statins as Modulators of Regulatory T-Cell Biology

Forero‐Peña, David A.; Gutierrez, Fredy R. S.

doi:10.1155/2013/167086

Cited by 69 publications

(51 citation statements)

References 64 publications

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“…Statins are best known for their capacity to inhibit cholesterol synthesis, but they also have anti-inflammatory effects by, for example, inhibiting leukocyte-endothelial adhesion, thereby muting the production of pro-inflammatory cytokines and modulating regulatory T cell activity 203,204 . Anecdotal stories suggest that local physicians in Sierra Leone successfully used two statins, atorvastatin and irbesartan 205 .…”

Section: Cytokine Stormmentioning

confidence: 99%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

111

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| The filoviruses -Ebola virus and Marburg virus -cause lethal haemorrhagic fever in humans and non-human primates (NHPs). Filoviruses present a global health threat both as naturally acquired diseases and as potential agents of bioterrorism. In the recent 2013-2016 outbreak of Ebola virus, the most promising therapies for post-exposure use with demonstrated efficacy in the gold-standard NHP models of filovirus disease were unable to show statistically significant protection in patients infected with Ebola virus. This Review briefly discusses these failures and what has been learned from these experiences, and summarizes the current status of post-exposure medical countermeasures in development, including antibodies, small interfering RNA and small molecules. We outline how our current knowledge could be applied to the identification of novel interventions and ways to use interventions more effectively. R E V I E W SNATURE REVIEWS | DRUG DISCOVERY VOLUME 17 | JUNE 2018 | 413 © 2 0 1 8 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d . AstheniaMuscular weakness. MyalgiaMuscular pain. ArthralgiaJoint pain. LeukopeniaA condition of having a low number of circulating leukocytes, including neutrophils, eosinophils, basophils, lymphocytes and monocytes. LymphocytopeniaA condition of having a low number of circulating leukocytes, including natural killer cells, T cells and B cells. ThrombocytopeniaA condition of having a low number of circulating thrombocytes, also known as platelets.and Ebolavirus. The Marburgvirus genus contains a single species, Marburg marburgvirus, which contains two members, Marburg virus (MARV) and Ravn virus (RAVV). The Ebolavirus genus consists of five distinct species: Bundibugyo ebolavirus (BDBV), Reston ebolavirus (RESTV), Sudan ebolavirus (SUDV), Tai Forest ebolavirus (TAFV; previously termed 'Côte d'Ivoire ebolavirus' but more commonly known as 'Ivory Coast ebolavirus') and Zaire ebolavirus (EBOV). MARV, RAVV, BDBV, SUDV and EBOV are important human pathogens, with case fatality rates often up to 90% for MARV, RAVV and EBOV, and around 55% for SUDV 8,10 . On the basis of two small outbreaks in 2007 and 2012, BDBV seems to be the least pathogenic, with a case fatality rate of about 40-48% 11,12 . In 1994, TAFV was associated with a number of deaths in chimpanzees and a single symptomatic but non-lethal human infection in the Republic of Côte d'Ivoire 13,14 . RESTV is lethal for macaques but is not thought to cause disease in humans 15 . An outbreak of RESTV was reported in pigs in the Philippines in 2008; however, it remains uncertain whether the disease observed in the pigs was caused by RESTV or other agents reported to have co-infected the animals 16 . Clinical manifestationsClinical and laboratory signs of disease caused by filovirus infection are nonspecific and usually associated with an incubation period of 2-21 days (mean 4-10 days) 8,17 . Illness begins with an abrupt onset of fever, astheni...

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Section: Cytokine Stormmentioning

confidence: 99%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

111

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“…Recent studies have increasingly highlighted the immunomodulatory role of statins (132–134); and shown in some diseases (other than NAFLD), its potential to interfere in the IL-17 axis, both by inhibiting the differentiation of Th17 cells, decreasing the production of IL-17 (62, 133, 135, 136), and inducing upregulation and recruitment of Treg (133, 137–139), shifting thus T cells response to Treg dominance (134, 140), which has an anti-inflammatory role and is a coordinator of immunologic tolerance (98, 99). This effect was also evident in atherosclerosis where the administration of statins was associated with the accumulation of T regulatory cells in atherosclerotic plaque (141, 142).…”

Section: Emerging and Potentials Therapeutics Agents Targeting The Immentioning

confidence: 99%

Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets

Paquissi

2016

Front. Immunol.

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Non-alcoholic fatty liver disease (NAFLD) is an increasing problem worldwide and is associated with negative outcomes such as cirrhosis, hepatocellular carcinoma, insulin resistance, diabetes, and cardiovascular events. Current evidence shows that the immune response has an important participation driving the initiation, maintenance, and progression of the disease. So, various immune imbalances, from cellular to cytokines levels, have been studied, either for better compression of the disease pathophysiology or as biomarkers for severity assessment and outcome prediction. In this article, we performed a thorough review of studies that evaluated the role of inflammatory/immune imbalances in the NAFLD. At the cellular level, we gave special focus on the imbalance between neutrophils and lymphocytes counts (the neutrophil-to-lymphocyte ratio), and that which occurs between T helper 17 (Th17) and regulatory T cells as emerging biomarkers. By extension, we reviewed the reflection of these imbalances at the molecular level through pro-inflammatory cytokines including those involved in Th17 differentiation (IL-6, IL-21, IL-23, and transforming growth factor-beta), and those released by Th17 cells (IL-17A, IL-17F, IL-21, and IL-22). We gave particular attention to the role of IL-17, either produced by Th17 cells or neutrophils, in fibrogenesis and steatohepatitis. Finally, we reviewed the potential of these pathways as new therapeutic targets in NAFLD.

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“…Statins, best known for lowering cholesterol, also have cholesterol-independent effects, and have been shown to improve endothelial dysfunction, 25-30 reduce vascular wall inflammation, 27, 29, 31-35 and decrease platelet aggregation, 28, 29 and may improve autonomic function and sympathetic reflex regulation. 36 We previously observed a potential benefit and favorable interaction between statin and higher vitamin D levels on migraine.…”

Section: Introductionmentioning

confidence: 99%

Simvastatin and vitamin D for migraine prevention: A randomized, controlled trial

Buettner

Nir

Bertisch

et al. 2015

Annals of Neurology

100

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Objective To assess efficacy and tolerability of simvastatin plus vitamin D for migraine prevention in adults with episodic migraine. Methods We performed a randomized, double-blind, placebo-controlled trial with a 12-week baseline period and 24-week intervention period in 57 adults with episodic migraine. Participants were randomly assigned to simvastatin 20 mg tablets twice daily plus vitamin D3 1000 international units capsules twice daily or matching placebo tablets and capsules. Results Compared to placebo, participants using simvastatin plus vitamin D3 demonstrated a greater decrease in number of migraine days from the baseline period to intervention weeks 1-12: a change of -8.0 (IQR: -15.0 to -2.0) days in the active treatment group versus +1.0 (IQR: 1.0 to +6.0) days in the placebo group, P<0.001; and to intervention weeks 13-24: a change of -9.0 (IQR: -13 to -5) days in the active group versus +3.0 (IQR: -1.0 to +5.0) days in the placebo group, P<0.001. In the active treatment group, 8 patients (25%) experienced 50% reduction in the number of migraine days at 12 weeks and 9 (29%) at 24 weeks post randomization. In comparison, only 1 patient (3%) in the placebo group (p=0.03) experienced such reduction. Adverse events were similar in both active treatment and placebo groups. Interpretation The results demonstrate that simvastatin plus vitamin D is effective for prevention of headache in adults with episodic migraine. Given statins ability to repair endothelial dysfunction, this economical approach may also reduce the increased risk for vascular diseases among migraineurs.

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Statins as Modulators of Regulatory T-Cell Biology

Cited by 69 publications

References 64 publications

Post-exposure treatments for Ebola and Marburg virus infections

Post-exposure treatments for Ebola and Marburg virus infections

Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets

Simvastatin and vitamin D for migraine prevention: A randomized, controlled trial

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