Short-term Treatment with Atorvastatin Selectively Decreases Lymphocyte Count
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Statins are a chemically related group used as lipid-lowering agents, studies confirmed that statins have additional pleiotropic, cholesterol independent, effects mediated by inhibition of isoprenoid synthesis with subsequent inhibition of the downstream signaling molecules like Rho, Rac, and Ras. However, different statin members might have a distinctive effect on the immune system; thereby having different peripheral and cardiovascular actions, such extra-hepatic effects impose the preferences of one statin over another. The present study aimed to identify the role of the short-term utilization of atorvastatin on leukocyte concentration as a representative in vivo marker for immunomodulation. Two widely used statin agents were included in the study- the lipophilic (atorvastatin) versus the hydrophilic (rosuvastatin) for comparison. Blood samples were withdrawn from the two statin groups, before and after therapy, and an automated differential white blood cell count was performed to determine the difference between the studied samples. The results showed that short-term use of atorvastatin, but not rosuvastatin, was associated with a selective reduction of lymphocyte count (p<0.0001). The study concluded that lymphocyte levels were reduced significantly after short-term use of atorvastatin; an effect which might need to be considered in certain immunological disease associated with cardiac ones.
Keywords
- Bonetti PO. Lerman LO. Napoli C. Lerman A. Statin effects beyond lipid lowering—are they clinically relevant?. European Heart Journal. 2003; 24(3): 225-48. doi.org.10.1016/S0195-668X(02)00419-0
- Cordle A. Koenigsknecht-Talboo J. Wilkinson B. Limpert A. Landreth G. Mechanisms of statin-mediated inhibition of small G-protein function. Journal of Biological Chemistry. 2005; 280(40): 34202-9. doi.org.10.1074/jbc.M505268200
- Qu H. Meng YY. Chai H. Liang F. Zhang JY. Gao ZY. Shi DZ. The effect of statin treatment on circulating coenzyme Q10 concentrations: an updated meta-analysis of randomized controlled trials. European Journal of Medical Research. 2018; 23(1): 1-0. doi.org.10.1186/s40001-018-0353-6
- Sokalska A. Hawkins AB. Yamaguchi T. Duleba AJ. Lipophilic statins inhibit growth and reduce invasiveness of human endometrial stromal cells. Journal of Assisted Reproduction and Genetics. 2019; 36(3): 535-41. doi.org.10.1007/s10815-018-1352-9
- Koushki K. Shahbaz SK. Mashayekhi K. Sadeghi M. Zayeri ZD. Taba MY. Banach M. Al-Rasadi K. Johnston TP. Sahebkar A. Anti-inflammatory action of statins in cardiovascular disease: the role of inflammasome and toll-like receptor pathways. Clinical Reviews in Allergy and Immunology. 2021; 60(2):175-99. doi.org.10.1007/s12016-020-08791-9
- Sorathia N. Al-Rubaye H. Zal B. The effect of statins on the functionality of CD4+ CD25+ FOXP3+ regulatory T-cells in acute coronary syndrome: a systematic review and meta-analysis of randomised controlled trials in Asian populations. European Cardiology Review. 2019; 14(2):123. doi.org.10.15420/ecr.2019.9.2
- Qin L. Xie X. Fang P. Lin J. Prophylactic simvastatin treatment modulates the immune response and increases survival of mice following induction of lethal sepsis. Journal of International Medical Research. 2019; 47(8):3850-9. doi.org.10.1177/0300060519858508.
- Henslee AB. Steele TA. Combination statin and chemotherapy inhibits proliferation and cytotoxicity of an aggressive natural killer cell leukemia. Biomarker Research. 2018; 6(1):1-1. doi.org.10.1186/s40364-018-0140-0
- Kong B. Wang X. Yang W. Zhao X. Zhang R. Wang Y. Effects of simvastatin on the function of splenic CD4+ and CD8+ T cells in sepsis mice. Immunologic Research. 2018; 66(3):355-66. doi.org.10.1007/s12026-018-8994-7
- Akula MK. Ibrahim MX. Ivarsson EG. Khan OM. Kumar IT. Erlandsson M. Karlsson C. Xu X. Brisslert M. Brakebusch C. Wang D. Protein prenylation restrains innate immunity by inhibiting Rac1 effector interactions. Nature Communications. 2019; 10(1):1-3. doi.org.10.1038/s41467-019-11606-x
- Adam O. Laufs U. Rac1-mediated effects of HMG-CoA reductase inhibitors (statins) in cardiovascular disease. Antioxidants and Redox Signaling. 2014; 20(8):1238-50. doi.org.10.1089/ars.2013.5526
- Dos Anjos PM. Volpe CM. Miranda TC. Nogueira-Machado JA. Atorvastatin Inhibited ROS Generation and Increased IL-1β And IL-6 Release by Mononuclear Cells from Diabetic Patients. Endocrine, Metabolic and Immune Disorders-Drug Targets (Formerly Current Drug Targets-Immune, Endocrine and Metabolic Disorders). 2019; 19(8):1207-15. doi.org.10.2174/1871530319666190617160349
- Blank N. Schiller M. Krienke S. Busse F. Schätz B. Ho AD. Kalden JR. Lorenz HM. Atorvastatin inhibits T cell activation through 3-hydroxy-3-methylglutaryl coenzyme A reductase without decreasing cholesterol synthesis. The Journal of Immunology. 2007; 179(6):3613-21. doi.org.10.4049/jimmunol.179.6.3613
- Krysiak R. Okopien B. Effect of simvastatin on hemostasis in patients with isolated hypertriglyceridemia. Pharmacology. 2013; 92(3-4):187-90. doi.org.10.1159/000341909
- Ghittoni R. Enea Lazzerini P. Laghi Pasini F. Baldari CT. T lymphocytes as targets of statins: molecular mechanisms and therapeutic perspectives. Inflammation and Allergy-Drug Targets. 2007; 6(1):3-16. doi.org.10.2174/187152807780077291
- Mach F. Statins as immunomodulatory agents. Circulation. 2004; 109(21):II- 15. doi.org.10.1161/01.CIR.0000129502.10459.fe
- Prinyakupt J. Pluempitiwiriyawej C. Segmentation of white blood cells and comparison of cell morphology by linear and naïve Bayes classifiers. Biomedical Engineering Online. 2015; 14(1):1-9. doi.org.10.1186/s12938-015-0037-1
- Tanaka T. Porter CM. Horvath-Arcidiacono JA. Bloom ET. Lipophilic statins suppress cytotoxicity by freshly isolated natural killer cells through modulation of granule exocytosis. International Immunology. 2007; 19(2):163-73. doi.org.10.1093/intimm/dxl133
- Gullu S. Emral R. Bastemir M. Parkes AB. Lazarus JH. In vivo and in vitro effects of statins on lymphocytes in patients with Hashimoto’s thyroiditis. European Journal of Endocrinology. 2005; 153(1):41-8. doi.org.10.1530/eje.1.01941
- Sirtori CR. The pharmacology of statins. Pharmacological Research. 2014; 88:3-11. doi.org.10.1016/j.phrs.2014.03.002
- Kramer PA. Ravi S. Chacko B. Johnson MS. Darley-Usmar VM. A review of the mitochondrial and glycolytic metabolism in human platelets and leukocytes: implications for their use as bioenergetic biomarkers. Redox Biology. 2014; 2:206-10. doi.org.10.1016/j.redox.2013.12.026
- Curry L. Almukhtar H. Alahmed J. Roberts R. Smith PA. Simvastatin inhibits L-type Ca2+-channel activity through impairment of mitochondrial function. Toxicological Sciences. 2019; 169(2):543-52. doi.org.10.1093/toxsci/kfz068
- Bulhak AA. Gourine AV. Gonon AT. Sjöquist PO. Valen G. Pernow J. Oral pre‐treatment with rosuvastatin protects porcine myocardium from ischaemia/reperfusion injury via a mechanism related to nitric oxide but not to serum cholesterol level. Acta Physiologica Scandinavica. 2005;183(2):151-9. doi.org.10.1111/j.1365-201X.2004.01392.x
- Severino A. Zara C. Campioni M. Flego D. Angelini G. Pedicino D. Giglio AF. Trotta F. Giubilato S. Pazzano V. Lucci C. Atorvastatin inhibits the immediate-early response gene EGR1 and improves the functional pro of CD4+ T-lymphocytes in acute coronary syndromes. Oncotarget. 2017; 8(11):17529. doi.org.10.18632/oncotarget.15420
- Turcato G. Sanchis-Gomar F. Cervellin G. Zorzi E. Sivero V. Salvagno GL. Tenci A. Lippi G. Evaluation of neutrophil-lymphocyte and platelet-lymphocyte ratios as predictors of 30-day mortality in patients hospitalized for an episode of acute decompensated heart failure. Journal of Medical Biochemistry. 2019; 38(4):452-60. doi.org. 10.2478/jomb-2018-0044
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