title: Effect of oral administration with pravastatin and atorvastatin on airway hyperresponsiveness and allergic reactions in asthmatic mice.
abstract: BACKGROUND
  Asthma 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.
  
  
  OBJECTIVE
  To investigate the therapeutic effect of oral statins on airway hyperresponsiveness and allergic reaction.
  
  
  METHODS
  BALB/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.
  
  
  RESULTS
  Both pravastatin and atorvastatin effectively reduced airway hyperresponsiveness. Pravastatin effectively suppressed both T(H)1- and T(H)2-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.
  
  
  CONCLUSIONS
  Oral administration of pravastatin or atorvastatin not only was able to inhibit T(H)1 inflammatory responses but also had therapeutic effects on airway hyperresponsiveness and T(H)2 allergic responses. These results seem to suggest that these drugs have potential as a nonimmunosuppressive therapy for asthma and allergic diseases.
authors.affiliation: Department of Pediatrics, Tri-Service General Hospital and School of Medicine, National Defense Medical Center, Taipei, Taiwan. h-cf@yahoo.com.tw
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Huang
authors.forename: Ho-Jen
authors.initials: HJ
authors.lastname: Peng
authors.forename: Chia-Chao
authors.initials: CC
authors.lastname: Wu
authors.forename: Wen-Tsung
authors.initials: WT
authors.lastname: Lo
authors.forename: Yu-Lueng
authors.initials: YL
authors.lastname: Shih
authors.forename: Tzee-Chung
authors.initials: TC
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D000069059:Atorvastatin; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D016207:Cytokines / Q000032:analysis; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006967:Hypersensitivity / Q000188:drug therapy*; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D017035:Pravastatin / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D018417:Th1 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007074:Immunoglobulin G; D011758:Pyrroles; D010047:Ovalbumin; D000069059:Atorvastatin; D017035:Pravastatin