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The cholesterol‐lowering drug, simvastatin, attenuates rhinovirus‐induced IP‐10 release from human monocytic cells
Author(s) -
Wickert Lisa,
Gern James,
Audhya Anjon,
Bertics Paul
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.846.1
Subject(s) - simvastatin , statin , medicine , pharmacology , chemokine , inflammation , immunology
Statin drugs (3‐hydroxy‐3‐methylglutaryl‐coenzyme A [HMG‐CoA] reductase inhibitors) are the treatment of choice for dyslipidemia, and can also modulate immune cell function. Dyslipidemia and obesity are risk factors for asthma, a disorder of chronic airway inflammation. As such, there is evidence that statin drugs may have beneficial effects on asthma. To determine whether statin drugs modify antiviral responses of human monocytic cells, we treated human primary blood monocytes and bronchoalveolar macrophages with simvastatin prior to challenge with human rhinovirus (HRV), which commonly provokes acute asthma exacerbations. In both cell types, 24 h pretreatment with simvastatin resulted in a 60% attenuation of HRV‐induced release of the chemokine interferon‐inducible protein (IP)‐10 as measured by ELISA. The addition of mevalonate, the product of HMG‐CoA reductase, is able to fully rescue IP‐10 release. Simvastatin also reduced HRV‐induced phosphorylation of signal transducer and activator of transcription (STAT)‐1, which is upstream of IP‐10 release, by 60% as detected by immunoblot. Our findings suggest that simvastatin blunts HRV‐induced chemokine secretion through inhibition of STAT signaling. In the context of asthma and dyslipidemia, statin drugs have the potential to curb the inflammatory response to HRV infection. Grant Funding Source : 5T32DK007665–20