Pravastatin attenuates allergic airway inflammation by suppressing antigen-sensitization, IL-17 production, and antigen-presentation in the lung

Mitsuru Imamura ¹, Katsuhide Okunishi ¹, Hiroshi Ohtsu ², Kazuyuki Nakagome ¹, Hiroaki Harada ¹, Ryoichi Tanaka ¹, Kazuhiko Yamamoto ¹ and Makoto Dohi ^1*

¹ Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Japan
² Department of Clinical Trial Data Management, Graduate School of Medicine, University of Tokyo, Japan

^* To whom correspondence should be addressed. E-mail: mdohi-tky{at}umin.ac.jp.

Accepted 22 August 2008

Abstract

Background: Statins are widely used to treat hyperlipidemia. Their immunosuppressive effect has recently been confirmed in various immune-mediated disease models. However, relatively few studies have been conducted on allergic inflammation, so the precise mechanisms of their actions against allergies have not been fully clarified. On the other hand, the role of interleukin (IL)-17 in immune responses has been recently highlighted, but whether statins affect IL-17 production has not been well studied. We examined the effect of pravastatin on allergic airway inflammation in a mouse model, then elucidated the mechanism of action, focusing on its effect on IL-17 production.

Methods: BALB/c mice were immunized with ovalbumin (OVA) and then challenged with OVA aerosol. Pravastatin was delivered by intraperitoneal injection during either the sensitization or the challenge.

Results: When delivered during systemic sensitization, pravastatin suppressed OVA-induced proliferation and production of Th2-type cytokines such as IL-5 in spleen cells ex vivo and in vitro. IL-17 production was also suppressed. Further, pavastatin delivered during the inhalation of OVA attenuated eosinophilic airway inflammation, OVA-specific IgE production in serum, and OVA-induced IL-17 production in the thoracic lymph node. We also found that pravastatin attenuated the antigen-presenting capacity of CD11c+ cells obtained from the OVA-challenged lung.

Conclusion: Pravastatin suppresses the systemic sensitization to allergen with a down-regulation of IL-17 production. It also suppresses an ongoing immune response in the airway partly by suppressing antigen-presentation in the lung. Therefore, statins could be a novel therapeutic option for treatment of asthma.