Objective. To determine if statins induce anti-inflammatory effects in upper airway inflammation. Mediators of innate and adaptive immunity regulate airway inflammation. Release of these mediators involves enzymatic conversion of polyunsaturated fatty acids into biologically active mediators, which can be blocked by statins. Although upper airway inflammation and chronic sinusitis occur in millions of patients with asthma worldwide, the anti-inflammatory effects of statins in upper airway inflammation have not been previously studied. Study Design. Laboratory research. Setting. Tertiary referral center. Subjects and Methods. Analysis of sinus tissues collected from patients with chronic rhinosinusitis revealed suppression of highly expressed inflammatory mediators in patients who were found to be on statins, suggesting that statins may induce anti-inflammatory effects. Therefore, the authors performed an in vitro study to determine if these anti-inflammatory effects were induced by statins. Cultured primary human airway epithelial cells were exposed to ambient air pollution particulates (PM) to trigger the inflammation, with and without statins, and the expression of inflammatory mediators was analyzed. Results. The authors found that expression of CCL5, CCL11, and IL13RA was suppressed in patients on statins. In vitro exposure to PM enhanced the expression of these mediators, while pretreatment with statins completely blocked these effects. Furthermore, the effects of statins were blocked by inhibition of the statin pathway using isopentenyl-5-pyrophosphate. Statins did not have any significant effect on the viability of normal cells. Conclusion. Statins induce anti-inflammatory effects in human airway epithelial inflammation. Statins may play a role in the treatment and prevention of chronic rhinosinusitis and pulmonary exacerbation of obstructive airway diseases.© American Academy of Otolaryngology - Head and Neck Surgery Foundation 2011.