Effect of oral administration with pravastatin and atorvastatin on airway hyperresponsiveness and allergic reactions in asthmatic mice

Abstract

BackgroundAsthma is characterized by airway hyperresponsiveness and remodeling. Pravastatin and atorvastatin are used clinically as cholesterol-lowering agents but also exhibit anti-inflammatory and immunomodulating properties. ObjectiveTo investigate the therapeutic effect of oral statins on airway hyperresponsiveness and allergic reaction. MethodsBALB/c mice received intraperitoneal sensitization and aerosol inhalation with ovalbumin consequently. One week after ovalbumin aerosol challenge, pravastatin, atorvastatin, or phosphate-buffered saline were given by intragastric gavage daily for 2 weeks. Airway hyperresponsiveness, serum allergen specific antibody levels, cytokine production by splenocytes, and bronchoalveolar lavage fluid were examined. ResultsBoth pravastatin and atorvastatin effectively reduced airway hyperresponsiveness. Pravastatin effectively suppressed both TH1- and TH2-mediated antibody responses, reducing serum specific IgE, IgG, IgG1, and IgG2a levels. Pravastatin also effectively reduced interleukin (IL) 4, IL-5, and interferon γ production but significantly enhanced IL-10 levels in splenocytes and BALF. Similarly, atorvastatin effectively attenuated production of specific IgE, IgG1, and IgG2a antibodies. It also significantly attenuated IL-4, interferon γ, and increased IL-10 concentration in bronchoalveolar lavage fluid and splenocytes. ConclusionOral administration of pravastatin or atorvastatin not only was able to inhibit TH1 inflammatory responses but also had therapeutic effects on airway hyperresponsiveness and TH2 allergic responses. These results seem to suggest that these drugs have potential as a nonimmunosuppressive therapy for asthma and allergic diseases.