title: Attenuation of airway inflammation by simvastatin and the implications for asthma treatment: is the jury still out?
abstract: Although some studies have explained the immunomodulatory effects of statins, the exact mechanisms and the therapeutic significance of these molecules remain to be elucidated. This study not only evaluated the therapeutic potential and inhibitory mechanism of simvastatin in an ovalbumin (OVA)-specific asthma model in mice but also sought to clarify the future directions indicated by previous studies through a thorough review of the literature. BALB/c mice were sensitized to OVA and then administered three OVA challenges. On each challenge day, 40 mg kg(-1) simvastatin was injected before the challenge. The airway responsiveness, inflammatory cell composition, and cytokine levels in bronchoalveolar lavage (BAL) fluid were assessed after the final challenge, and the T cell composition and adhesion molecule expression in lung homogenates were determined. The administration of simvastatin decreased the airway responsiveness, the number of airway inflammatory cells, and the interleukin (IL)-4, IL-5 and IL-13 concentrations in BAL fluid compared with vehicle-treated mice (P<0.05). Histologically, the number of inflammatory cells and mucus-containing goblet cells in lung tissues also decreased in the simvastatin-treated mice. Flow cytometry showed that simvastatin treatment significantly reduced the percentage of pulmonary CD4(+) cells and the CD4(+)/CD8(+) T-cell ratio (P<0.05). Simvastatin treatment also decreased the expression of the vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 proteins, as measured in homogenized lung tissues (P<0.05) and human epithelial cells. The reduction in the T cell influx as a result of the decreased expression of cell adhesion molecules is one of the mechanisms by which simvastatin attenuates airway responsiveness and allergic inflammation. Rigorous review of the literature together with our findings suggested that simvastatin should be further developed as a potential therapeutic strategy for allergic asthma.
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Jing-Nan
authors.initials: JN
authors.lastname: Liu
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Dong-Hyeon
authors.initials: DH
authors.lastname: Suh
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Yang
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Seung-Ihm
authors.initials: SI
authors.lastname: Lee
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Yoo Seob
authors.initials: YS
authors.lastname: Shin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D007378:Interleukins / Q000032:analysis / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D008807:Mice, Inbred BALB C; D019821:Simvastatin / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007378:Interleukins; D019821:Simvastatin