Simvastatin-induced effects on bronchial epithelial cells from COPD donors.

I read with interest the report by LEE et al. [1] on inhibition by simvastatin of double-stranded (ds)RNA-induced bronchial epithelial cell production of RANTES, with supportive in vivo data in mice. dsRNA is an interesting challenge agent. It not only mimics viral infection, as noted by LEE et al. [1], but may also reflect effects of released mRNA or secondary structure from necrotic cells that commonly occur in severe bronchial diseases (for references, see [2]). RANTES, similar to interferon (IFN)-b, is induced by activation of the transcription factor IRF3 (IFN regulatory factor 3) [3]. Hence, the anti-RANTES effect demonstrated by LEE et al. [1] may agree with our current demonstration of simvastatin-induced inhibition of IRF3 phosphorylation in dsRNA-challenged bronchial epithelial cells; we used primary cells obtained by bronchial brushings in chronic obstructive pulmonary disease (COPD) patients [4]. We further showed that the inhibition of IRF3 activation occurred without effects on nuclear factor (NF)-kB. As expected then, simvastatin inhibited IFN-b gene expression and protein production without reducing NF-kB-dependent cytokines, such as tumour necrosis factor-a and CXCL8 [4]. Inhibition of IFN-b, a major antiviral IFN, needs consideration by investigators who may wish to explore anti-RANTES effects of simvastatin in patients with respiratory diseases.