Lovastatin treatment mitigates the pro-inflammatory cytokine response in respiratory syncytial virus infected macrophage cells

Abstract

Disease severity following respiratory syncytial virus (RSV) infection is associated with inflammation due to enhanced pro-inflammatory cytokine secretion, and lung macrophage cells play a role in this process. In this study we evaluated the hydroxymethylglutaryl coenzyme A reductase inhibitor lovastatin as an anti-inflammatory drug to control RSV-induced cytokine secretion in the murine RAW 264.7 (RAW) macrophage cell line and in primary murine lung macrophages. These cells could be efficiently infected with RSV in vitro, and although no significant level of infectious virus particles were produced, the increased expression of several virus structural proteins could be detected. Virus infection and gene expression correlated with increased pro-inflammatory cytokine secretion by 24h post infection. Lovastatin treatment did not reduce the cellular cholesterol levels in RSV-infected cells, nor did it inhibit RSV infection. However, we observed a significant reduction in the pro-inflammatory cytokine levels in lovastatin-treated RSV-infected cells. Since enhanced pro-inflammatory cytokine secretion is a major factor in RSV-associated pathology our findings highlighted the potential use of statins to mitigate and control the inflammatory response due to RSV infection. Furthermore, our study suggested that RAW cells maybe a simple and cost-effective model cell system to screen small molecule libraries to identify compounds that are effective in reducing RSV-induced inflammation.