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J Leukoc Biol. 2014 Jun;95(6):951-9. doi: 10.1189/jlb.0713413. Epub 2014 Feb 14.

Simvastatin attenuates rhinovirus-induced interferon and CXCL10 secretion from monocytic cells in vitro.

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  • 1Departments of Biomolecular Chemistry, Nutritional Sciences, and
  • 2Departments of Biomolecular Chemistry.
  • 3Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.


RV infections frequently trigger exacerbations of respiratory diseases, such as asthma, yet treatment and intervention options remain limited. Statin drugs are the treatment of choice for dyslipidemia and can also modulate immune cell function. To determine whether statin drugs modify antiviral responses of human monocytic cells, we obtained blood monocytes from donors with allergies and/or asthma and treated the cells with sim prior to challenge with RV. RV-induced secretion of CXCL10 was attenuated significantly, irrespective of RV type (RV-16, -14, or -1A), which corresponded with decreases in IFN-α secretion and pSTAT1. Sim pretreatment also reduced RV-induced CXCL10 secretion from human alveolar macrophages. The addition of mev and GGPP-two intermediates of the cholesterol biosynthesis pathway-was able to rescue CXCL10 release fully, demonstrating that effects of sim were related to inhibition of cholesterol biosynthesis and not to an off-target effect. In addition, sim pretreatment attenuated IFN-α-induced pSTAT1 and CXCL10 secretion, providing evidence that sim additionally can affect type I IFNR signaling. SOCS1 and 3 mRNA are both induced with RV stimulation, but sim did not elevate SOCS1 or SOCS3 mRNA expression basally or in the presence of RV. Our findings suggest that sim inhibition of the cholesterol biosynthesis pathway leads to decreased RV-induced chemokine secretion in monocytes and macrophages. These findings suggest that statin drugs have the potential to curb the inflammatory response to RV infection.

© 2014 Society for Leukocyte Biology.


chemokines; inflammation; macrophages; statins; virus

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