Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2014, Article ID 872370, 8 pages
http://dx.doi.org/10.1155/2014/872370
Review Article

Mechanisms of Action and Efficacy of Statins against Influenza

1Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
2Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

Received 6 June 2014; Revised 8 September 2014; Accepted 10 September 2014; Published 11 November 2014

Academic Editor: Kelvin To

Copyright © 2014 Parvaneh Mehrbod et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. E. J. Armstrong and P. K. Safo, “Pharmacology of cholesterol and lipoprotein metabolism,” in Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy, pp. 369–389, Lippincott Williams & Wilkins, Baltimore, Md, USA, 2005. View at Google Scholar
  2. A. Endo, “The discovery and development of HMG-CoA reductase inhibitors,” Journal of Lipid Research, vol. 33, no. 11, pp. 1569–1582, 1992. View at Google Scholar · View at Scopus
  3. I. Darwish, S. Mubareka, and W. C. Liles, “Immunomodulatory therapy for severe influenza,” Expert Review of Anti-Infective Therapy, vol. 9, no. 7, pp. 807–822, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. X. Sun and G. R. Whittaker, “Role for influenza virus envelope cholesterol in virus entry and infection,” Journal of Virology, vol. 77, no. 23, pp. 12543–12551, 2003. View at Publisher · View at Google Scholar · View at Scopus
  5. J. L. Goldstein and M. S. Brown, “Regulation of the mevalonate pathway,” Nature, vol. 343, no. 6257, pp. 425–430, 1990. View at Publisher · View at Google Scholar · View at Scopus
  6. L. M. Blanco-Colio, J. Tuñón, J. L. Martín-Ventura, and J. Egido, “Anti-inflammatory and immunomodulatory effects of statins,” Kidney International, vol. 63, no. 1, pp. 12–23, 2003. View at Publisher · View at Google Scholar · View at Scopus
  7. U. Laufs, M. Endres, F. Custodis et al., “Suppression of endothelial nitric oxide production after withdrawal of statin treatment is mediated by negative feedback regulation of rho GTPase gene transcription,” Circulation, vol. 102, no. 25, pp. 3104–3110, 2000. View at Publisher · View at Google Scholar · View at Scopus
  8. P. J. Casey, P. A. Solski, C. J. Der, and J. E. Buss, “p21ras is modified by a farnesyl isoprenoid,” Proceedings of the National Academy of Sciences of the United States of America, vol. 86, no. 21, pp. 8323–8327, 1989. View at Publisher · View at Google Scholar · View at Scopus
  9. J. K. Liao and U. Laufs, “Pleiotropic effects of statins,” Annual Review of Pharmacology and Toxicology, vol. 45, pp. 89–118, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Terblanche, Y. Almog, R. S. Rosenson, T. S. Smith, and D. G. Hackam, “Statins and sepsis: multiple modifications at multiple levels,” The Lancet Infectious Diseases, vol. 7, no. 5, pp. 358–368, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. S. E. Alexeeff, A. A. Litonjua, D. Sparrow, P. S. Vokonas, and J. Schwartz, “Statin use reduces decline in lung function: VA normative aging study,” American Journal of Respiratory and Critical Care Medicine, vol. 176, no. 8, pp. 742–747, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. P. Mehrbod, M. El Zowalaty, A. R. Omar, M. Hair-Bejo, and A. Ideris, “Statins reduce the expression of proinflammatory cytokines in influenza A virus infected CrFK cells,” Acta Virologica, vol. 56, no. 4, pp. 353–355, 2012. View at Publisher · View at Google Scholar · View at Scopus
  13. K. L. Watts, E. M. Sampson, G. S. Schultz, and M. A. Spiteri, “Simvastatin inhibits growth factor expression and modulates profibrogenic markers in lung fibroblasts,” American Journal of Respiratory Cell and Molecular Biology, vol. 32, no. 4, pp. 290–300, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. C. S. Lee, E. H. Yi, J.-K. Lee et al., “Simvastatin suppresses RANTES-mediated neutrophilia in polyinosinic-polycytidylic acid-induced pneumonia,” European Respiratory Journal, vol. 41, no. 5, pp. 1147–1156, 2013. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Blanc, W. Y. Hsieh, K. A. Robertson et al., “Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis,” PLoS Biology, vol. 9, no. 3, Article ID e1000598, 2011. View at Publisher · View at Google Scholar · View at Scopus
  16. D. S. Fedson, “Pandemic influenza: a potential role for statins in treatment and prophylaxis,” Clinical Infectious Diseases, vol. 43, no. 2, pp. 199–205, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Terblanche, T. S. Smith, and N. K. J. Adhikari, “Statins, bugs and prophylaxis: intriguing possibilities,” Critical Care, vol. 10, no. 5, article 168, 2006. View at Publisher · View at Google Scholar · View at Scopus
  18. E. R. Campagnolo, J. T. Rankin, S. A. Daverio et al., “Fatal pandemic (H1N1) 2009 influenza A virus infection in a pennsylvania domestic cat,” Zoonoses and Public Health, vol. 58, no. 7, pp. 500–507, 2011. View at Publisher · View at Google Scholar · View at Scopus
  19. R. J. Garten, C. T. Davis, C. A. Russell et al., “Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans,” Science, vol. 325, no. 5937, pp. 197–201, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. M. D. de Jong, C. P. Simmons, T. T. Thanh et al., “Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia,” Nature Medicine, vol. 12, no. 10, pp. 1203–1207, 2006. View at Publisher · View at Google Scholar · View at Scopus
  21. G. Lippi, M. Franchini, and E. J. Favaloro, “Influenza and cardiovascular disease: does swine-origin, 2009 H1N1 flu virus represent a risk factor, an acute trigger, or both?” Seminars in Thrombosis and Hemostasis, vol. 36, no. 1, pp. 49–58, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. C. Y. Cheung, L. L. M. Poon, A. S. Lau et al., “Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease?” The Lancet, vol. 360, no. 9348, pp. 1831–1837, 2002. View at Publisher · View at Google Scholar · View at Scopus
  23. A. S. Lipatov, S. Andreansky, R. J. Webby et al., “Pathogenesis of Hong Kong H5N1 influenza virus NS gene reassortants in mice: the role of cytokines and B- and T-cell responses,” Journal of General Virology, vol. 86, no. 4, pp. 1121–1130, 2005. View at Publisher · View at Google Scholar · View at Scopus
  24. M. T. Osterholm, “Preparing for the next pandemic,” New England Journal of Medicine, vol. 352, no. 18, pp. 1839–1842, 2005. View at Publisher · View at Google Scholar · View at Scopus
  25. F. J. Frost, H. Petersen, K. Tollestrup, and B. Skipper, “Influenza and COPD mortality protection as pleiotropic, dose-dependent effects of statins,” Chest, vol. 131, no. 4, pp. 1006–1012, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. J. C. Kwong, P. Li, and D. A. Redelmeier, “Influenza morbidity and mortality in elderly patients receiving statins: a cohort study,” PLoS ONE, vol. 4, no. 11, Article ID e0008087, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. D. M. Fleming, N. Q. Verlander, A. J. Elliot et al., “An assessment of the effect of statin use on the incidence of acute respiratory infections in England during winters 1998–1999 to 2005–2006,” Epidemiology and Infection, vol. 138, pp. 1–8, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. R. Carrillo-Esper, J. Ojino Sosa-García, and E. Arch-Tirado, “Experience in the management of the severe form of human influenza A H1N1 pneumonia in an intensive care unit,” Cirugia y Cirujanos, vol. 79, no. 5, pp. 409–416, 2011. View at Google Scholar · View at Scopus
  29. D. Viasus, J. Ramón Paño-Pardo, E. Cordero et al., “Effect of immunomodulatory therapies in patients with pandemic influenza A (H1N1) 2009 complicated by pneumonia,” Journal of Infection, vol. 62, no. 3, pp. 193–199, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. D. Makris, E. Manoulakas, A. Komnos et al., “Effect of pravastatin on the frequency of ventilator-associated pneumonia and on intensive care unit mortality: open-label, randomized study,” Critical Care Medicine, vol. 39, no. 11, pp. 2440–2446, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. S. Yende, E. B. Milbrandt, J. A. Kellum et al., “Understanding the potential role of statins in pneumonia and sepsis,” Critical Care Medicine, vol. 39, no. 8, pp. 1871–1878, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. M. L. Vandermeer, A. R. Thomas, L. Kamimoto et al., “Association between use of statins and mortality among patients hospitalized with laboratory-confirmed influenza virus infections: a multistate study,” Journal of Infectious Diseases, vol. 205, no. 1, pp. 13–19, 2012. View at Publisher · View at Google Scholar · View at Scopus
  33. L. Papazian, A. Roch, P.-E. Charles et al., “Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial,” Journal of the American Medical Association, vol. 310, no. 16, pp. 1692–1700, 2013. View at Publisher · View at Google Scholar · View at Scopus
  34. P. Kruger, M. Bailey, R. Bellomo et al., “A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis,” American Journal of Respiratory and Critical Care Medicine, vol. 187, no. 7, pp. 743–750, 2013. View at Publisher · View at Google Scholar · View at Scopus
  35. I. M. Lagoja and E. de Clercq, “Anti-influenza virus agents: synthesis and mode of action,” Medicinal Research Reviews, vol. 28, no. 1, pp. 1–38, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. A. Moscona, “Global transmission of oseltamivir-resistant influenza,” New England Journal of Medicine, vol. 360, no. 10, pp. 953–956, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. M. Baz, Y. Abed, J. Papenburg, X. Bouhy, M. È. Hamelin, and G. Boivin, “Emergence of oseltamivir-resistant pandemic H1N1 virus during prophylaxis,” The New England Journal of Medicine, vol. 361, no. 23, pp. 2296–2297, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. A. E. Fiore, D. K. Shay, K. Broder et al., “Prevention and control of influenza: recommendations of the advisory committee on immunization practices,” Recommendations and Reports, vol. 57, no. 7, pp. 1–60, 2008. View at Google Scholar · View at Scopus
  39. D. S. Fedson, “Confronting an influenza pandemic with inexpensive generic agents: can it be done?” The Lancet Infectious Diseases, vol. 8, no. 9, pp. 571–576, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. M. Haidari, A. Muzammil, S. W. Casscells, and M. Madjid, “Statins block influenza infection by down-regulating Rho/Rho kinase pathway,” Circulation, vol. 116, pp. 116–117, 2007. View at Google Scholar
  41. S. Ludwig, “Disruption of virus-host cell interactions and cell signaling pathways as an anti-viral approach against influenza virus infections,” Biological Chemistry, vol. 392, no. 10, pp. 837–847, 2011. View at Publisher · View at Google Scholar · View at Scopus
  42. M. Haidari, W. Zhang, L. Ganjehei, M. Ali, and Z. Chen, “Inhibition of MLC phosphorylation restricts replication of influenza virus-a mechanism of action for anti-influenza agents,” PLoS ONE, vol. 6, no. 6, Article ID e21444, 2011. View at Publisher · View at Google Scholar · View at Scopus
  43. G. R. Whittaker, “Intracellular trafficking of influenza virus: clinical implications for molecular medicine,” Expert Reviews in Molecular Medicine, vol. 3, pp. 1–13, 2001. View at Publisher · View at Google Scholar
  44. D. S. Hui and N. Lee, “Adjunctive therapies and immunomodulating agents for severe influenza,” Influenza and other Respiratory Viruses, vol. 7, no. 3, pp. 52–59, 2013. View at Publisher · View at Google Scholar · View at Scopus
  45. L. M. Alleva, R. C. Gualano, and I. A. Clark, “Current work and future possibilities for the management of severe influenza: Using immunomodulatory agents that target the host response,” Future Virology, vol. 6, no. 7, pp. 843–854, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. P. Mehrbod, A. Ideris, A. R. Omar, and M. Hair-Bejo, “Evaluation of antiviral effect of atorvastatin on H1N1 infection in MDCK cells,” African Journal of Microbiology Research, vol. 6, no. 27, pp. 5715–5719, 2012. View at Google Scholar
  47. P. Mehrbod, M. Hair-Bejo, T. A. Tengku Ibrahim et al., “Simvastatin modulates cellular components in influenza A virus-infected cells,” International Journal of Molecular Medicine, vol. 34, no. 1, pp. 61–73, 2014. View at Publisher · View at Google Scholar
  48. T. L. Gower and B. S. Graham, “Antiviral activity of lovastatin against respiratory syncytial virus in vivo and in vitro,” Antimicrobial Agents and Chemotherapy, vol. 45, no. 4, pp. 1231–1237, 2001. View at Publisher · View at Google Scholar · View at Scopus
  49. J. R. Jacobson, J. W. Barnard, D. N. Grigoryev, S.-F. Ma, R. M. Tuder, and J. G. N. Garcia, “Simvastatin attenuates vascular leak and inflammation in murine inflammatory lung injury,” American Journal of Physiology—Lung Cellular and Molecular Physiology, vol. 288, no. 6, pp. L1026–L1032, 2005. View at Publisher · View at Google Scholar · View at Scopus
  50. S. A. Ferraro, J. S. Yakisich, F. T. Gallo, and D. R. Tasat, “Simvastatin pretreatment prevents ambient particle-induced lung injury in mice,” Inhalation Toxicology, vol. 23, no. 14, pp. 889–896, 2011. View at Publisher · View at Google Scholar · View at Scopus
  51. S.-C. An, L.-L. Xu, F.-D. Li, L.-L. Bao, C. Qin, and Z.-C. Gao, “Triple combinations of neuraminidase inhibitors, statins and fibrates benefit the survival of patients with lethal avian influenza pandemic,” Medical Hypotheses, vol. 77, no. 6, pp. 1054–1057, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. Y. Kumaki, J. D. Morrey, and D. L. Barnard, “Effect of statin treatments on highly pathogenic avian influenza H5N1, seasonal and H1N1pdm09 virus infections in BALB/c mice,” Future Virology, vol. 7, no. 8, pp. 801–818, 2012. View at Publisher · View at Google Scholar · View at Scopus
  53. K. A. Radigan, D. Urich, A. V. Misharin et al., “The effect of rosuvastatin in a murine model of influenza a infection,” PLoS ONE, vol. 7, no. 4, Article ID e35788, 2012. View at Publisher · View at Google Scholar · View at Scopus
  54. R. Salomon, E. Hoffmann, and R. G. Webster, “Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 30, pp. 12479–12481, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. K. J. Szretter, S. Gangappa, X. Lu et al., “Role of host cytokine responses in the pathogenesis of avian H5N1 influenza viruses in mice,” Journal of Virology, vol. 81, no. 6, pp. 2736–2744, 2007. View at Publisher · View at Google Scholar · View at Scopus
  56. Z. Liu, Z. Guo, G. Wang et al., “Evaluation of the efficacy and safety of a statin/caffeine combination against H5N1, H3N2 and H1N1 virus infection in BALB/c mice,” European Journal of Pharmaceutical Sciences, vol. 38, no. 3, pp. 215–223, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. L. A. Horrigan, J. P. Kelly, and T. J. Connor, “Immunomodulatory effects of caffeine: friend or foe?” Pharmacology and Therapeutics, vol. 111, no. 3, pp. 877–892, 2006. View at Publisher · View at Google Scholar · View at Scopus
  58. N. L. Benowitz, “Clinical pharmacology of caffeine,” Annual Review of Medicine, vol. 41, no. 1, pp. 277–288, 1990. View at Publisher · View at Google Scholar · View at Scopus
  59. B. Renner, G. Clarke, T. Grattan et al., “Caffeine accelerates absorption and enhances the analgesic effect of acetaminophen,” Journal of Clinical Pharmacology, vol. 47, no. 6, pp. 715–726, 2007. View at Publisher · View at Google Scholar · View at Scopus
  60. J. A. Belser, K. J. Szretter, J. M. Katz, and T. M. Tumpey, “Simvastatin and oseltamivir combination therapy does not improve the effectiveness of oseltamivir alone following highly pathogenic avian H5N1 influenza virus infection in mice,” Virology, vol. 439, no. 1, pp. 42–46, 2013. View at Publisher · View at Google Scholar · View at Scopus
  61. B. Glück, M. Schmidtke, M. Walther, A. Meerbach, and P. Wutzler, “Simvastatin treatment showed no prophylactic effect in influenza virus-infected mice,” Journal of Medical Virology, vol. 85, no. 11, pp. 1978–1982, 2013. View at Publisher · View at Google Scholar · View at Scopus
  62. M. B. Fessler, S. K. Young, S. Jeyaseelan et al., “A role for hydroxy-methylglutaryl coenzyme A reductase in pulmonary inflammation and host defense,” American Journal of Respiratory and Critical Care Medicine, vol. 171, no. 6, pp. 606–615, 2005. View at Publisher · View at Google Scholar · View at Scopus
  63. S. J. Brett, P. Myles, W. S. Lim et al., “Pre-admission statin use and in-hospital severity of 2009 pandemic influenza A(H1N1) disease,” PLoS ONE, vol. 6, no. 4, Article ID e18120, 2011. View at Publisher · View at Google Scholar · View at Scopus
  64. M. Enserink, “Old drugs losing effectiveness against flu; could statins fill gap?” Science, vol. 309, no. 5743, pp. 1976–1977, 2005. View at Google Scholar · View at Scopus
  65. S. Janda, A. Young, J. M. FitzGerald, M. Etminan, and J. Swiston, “The effect of statins on mortality from severe infections and sepsis: a systematic review and meta-analysis,” Journal of Critical Care, vol. 25, no. 4, pp. 656.e7–656.e22, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. M. E. Falagas, G. C. Makris, D. K. Matthaiou, and P. I. Rafailidis, “Statins for infection and sepsis: a systematic review of the clinical evidence,” Journal of Antimicrobial Chemotherapy, vol. 61, no. 4, pp. 774–785, 2008. View at Publisher · View at Google Scholar · View at Scopus
  67. P. Kopterides and M. E. Falagas, “Statins for sepsis: a critical and updated review,” Clinical Microbiology and Infection, vol. 15, no. 4, pp. 325–334, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. A. R. Boyd and E. M. Mortensen, “Are statins beneficial for viral pneumonia?” European Respiratory Journal, vol. 41, no. 5, pp. 1010–1011, 2013. View at Publisher · View at Google Scholar · View at Scopus
  69. F. G. Hayden, “Newer influenza antivirals, biotherapeutics and combinations,” Influenza and other Respiratory Viruses, vol. 7, supplement 1, pp. 63–75, 2013. View at Publisher · View at Google Scholar · View at Scopus