Anti-inflammatory activity of statins in asthma and copd

Abstract

Statins are conventionally known as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that deplete mevalonic acid. Statins possess pleiotropic effects on the inhibition of multiple inflammatory signals independent of their cholesterol-lowering capacity. Statins suppress mevalonic acid-induced smooth muscle proliferation. In animal studies, statins could inhibit eosinophilic and neutrophilic airway inflammation, a key pathology of asthma and COPD respectively, by modulating a variety of signal transductions. These include the inhibition of guanosine triphosphatase, nuclear factor-κB mediated activation of inflammatory / matrix remodelling pathways, and p38 MAPK mediated eosinophilic inflammation. In addition, statins attenuate airway remodeling, particularly the suppression of airway smooth muscle hyperplasia, and therefore improve airway hyperresponsiveness in asthma. Clinical studies suggested that statins enhance anti-inflammatory effects of corticosteroids on eosinophilic airway inflammation in asthma through the induction of the immunosuppressive indoleamine 2, 3-dioxygenase activity and the release of an anti-inflammatory cytokine, IL-10. Statins also mediate their effective anti-inflammatory effects through the suppression of the mevalonic acid cascade in alveolar macrophages that have emerged as critical modulators in the COPD pathophysiology. This chapter provides the proposed molecular mechanisms underlying the anti-inflammatory / anti-airway remodeling actions and the clinical effectiveness of statins in both asthma and COPD. © 2012 by Nova Science Publishers, Inc. All rights reserved.