Pirfenidone modulates airway responsiveness, inflammation, and remodeling after repeated challenge

Am J Respir Cell Mol Biol. 2006 Sep;35(3):366-77. doi: 10.1165/rcmb.2005-0452OC. Epub 2006 May 4.

Abstract

We investigated the therapeutic potential of a newly developed antifibrotic agent, pirfenidone, to regulate airway remodeling and the development of allergic airway inflammation and airway hyperresponsiveness after chronic allergen challenge. Administration of pirfenidone after sensitization but during the period of ovalbumin challenge significantly prevented the development of airway hyperresponsiveness and prevented eosinophil and lymphocyte accumulation in the airways. IL-4, IL-5, and IL-13 levels in bronchoalveolar lavage fluid and ovalbumin-specific serum IgE antibody levels were also significantly reduced. Treatment with pirfenidone significantly reduced transforming growth factor-beta1 and platelet-derived growth factor levels in bronchoalveolar lavage fluid. Pirfenidone reduced the expression of transforming growth factor-beta1, the development of goblet cell hyperplasia and subepithelial collagenization, and the increases in contractile elements in the lung. These data indicate that pirfenidone may play an important role in the treatment of asthma and has the potential reduce or prevent airway remodeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Allergens / immunology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / immunology
  • Asthma / pathology
  • Bronchial Hyperreactivity / drug therapy*
  • Bronchial Hyperreactivity / immunology
  • Bronchial Hyperreactivity / pathology
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cell Proliferation / drug effects
  • Cytokines / metabolism
  • Eosinophils / immunology
  • Goblet Cells / drug effects
  • Goblet Cells / pathology
  • Hyperplasia
  • Immunoglobulin E / blood
  • Interleukin-13 / analysis
  • Interleukin-4 / analysis
  • Interleukin-5 / analysis
  • Leukocytes, Mononuclear / drug effects
  • Lymphocytes / immunology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / immunology
  • Platelet-Derived Growth Factor / analysis
  • Pyridones / pharmacology
  • Pyridones / therapeutic use*
  • Transforming Growth Factor beta / analysis
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta1

Substances

  • Allergens
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Interleukin-13
  • Interleukin-5
  • Platelet-Derived Growth Factor
  • Pyridones
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Interleukin-4
  • Immunoglobulin E
  • Ovalbumin
  • pirfenidone