Effect of Atorvastatin on PM10-induced Cytokine Production by Human Alveolar Macrophages and Bronchial Epithelial Cells

Exposure to ambient air pollution particles (PM10) has been associated with increased cardiovascular morbidity and mortality. Inhaled pollutants induce a pulmonary and systemic inflammatory response that is thought to exacerbate cardiovascular disease. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to have anti-inflammatory effects that could contribute to their beneficial effect in cardiovascular disease. The aim of this study is to determine the effects of statins on PM10-induced cytokine production in human bronchial epithelial cells (HBECs) and alveolar macrophages (AMs). Primary HBECs and AMs are obtained from resected human lung. Cells are pre-treated with different concentrations of atorvastatin for 24 hours and then exposed to 100 mu g/mL urban air pollution particles (EHC-93). Cytokine levels (interleukin-1 beta, interleukin-8, granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha) are measured at messenger RNA and protein levels using real-time polymerase chain reaction and bead-based multiplex immunoassay, respectively. PM10 exposure increases production of these cytokines by both cell types. Atorvastatin attenuates PM10-induced messenger RNA expression and cytokine production by AMs but not by HBECs. It is concluded that statins can modulate the PM10-induced inflammatory response in the lung by reducing mediator production by AMs.