Anti-inflammatory mechanism of simvastatin in mouse allergic asthma model

Eur J Pharmacol. 2007 Feb 14;557(1):76-86. doi: 10.1016/j.ejphar.2006.11.027. Epub 2006 Nov 15.


Statins have anti-inflammatory property and immunomodulatory activity. In this study we aimed to investigate the inhibitory mechanism of simvastatin in allergic asthmatic symptoms in mice. BALB/c mice were sensitized and challenged by ovalbumin to induce asthma. Ovalbumin-specific serum IgE levels were measured by enzyme-linked immunosorbent assay (ELISA), and the recruitment of inflammatory cells into bronchoalveolar lavage fluid or lung tissues was measured by Diff-Quik staining and hematoxylin and eosin (H&E) staining, respectively, the expressions of CD40, CD40 ligand (CD40L), and vascular cell adhesion molecule-1 (VCAM-1) by immunohistochemistry, the mRNA and protein expressions of cytokines in lung tissues by reverse transcriptase-polymerase chain reaction (RT-PCR) or ELISA, epithelial hyperplasia by periodic acid-Schiff (PAS) staining, activities of matrix metalloproteinases (MMPs) by zymography, the activities of small G proteins, mitogen-activated protein (MAP) kinases and nuclear factor-kappa B (NF-kappaB) in bronchoalveolar lavage cells and lung tissues by western blot and EMSA, respectively. Simvastatin reduced ovalbumin-specific IgE level, the number of total inflammatory cells, macrophages, neutrophils, and eosinophils into bronchoalveolar lavage fluid, the expressions of CD40, CD40L or VCAM-1, the mRNA and protein levels of interleukin (IL)-4, IL-13 and tumor necrosis factor (TNF)-alpha, the numbers of goblet cells, activities of MMPs, and further small G proteins, MAP kinases and NF-kappaB activities in bronchoalveolar lavage cells and lung tissues increased in ovalbumin-induced allergic asthma in mice. Our data suggest that simvastatin may be used as a therapeutic agent in asthma, based on reductions of various allergic responses via regulating small G proteins/MAP kinases/NF-kappaB in mouse allergic asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Asthma / chemically induced
  • Asthma / drug therapy*
  • Asthma / metabolism
  • Asthma / pathology
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • CD40 Antigens / metabolism
  • CD40 Ligand / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • GTP-Binding Proteins / metabolism
  • Immunoglobulin E / blood
  • Leukocyte Count
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Ovalbumin
  • RNA, Messenger / metabolism
  • Simvastatin / pharmacology*
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Anti-Inflammatory Agents
  • CD40 Antigens
  • Cytokines
  • NF-kappa B
  • RNA, Messenger
  • Vascular Cell Adhesion Molecule-1
  • CD40 Ligand
  • Immunoglobulin E
  • Ovalbumin
  • Simvastatin
  • Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinases
  • GTP-Binding Proteins