Interleukin-1 receptor antagonist attenuates airway hyperresponsiveness following exposure to ozone

Jung Won Park, Christian Taube, Christina Swasey, Taku Kodama, Anthony Joetham, Annette Balhorn, Katsuyuki Takeda, Nobuaki Miyahara, Corrie B. Allen, Azzeddine Dakhama, Soo Hyun Kim, Charles A. Dinarello, Erwin W. Gelfand

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Abstract

The role of an interleukin (IL)-1 receptor antagonist (IL-1Ra) on the development of airway hyperresponsiveness (AHR) and airway inflammation following acute O3 exposure in mice was investigated. Exposure of C57/BL6 mice to O3 at a concentration of 2.0 ppm or filtered air for 3 h resulted in increases in airway responsiveness to inhaled methacholine (MCh) 8 and 16 h after the exposure, and an increase in neutrophils in the bronchoalveolar lavage (BAL) fluid. IL-1β expression, assessed by gene microarray, was increased 2-fold 4 h after O3 exposure, and returned to baseline levels by 24 h. Levels of IL-1β in lung homogenates were also increased 8 h after O3 exposure. Administration of (human) IL-1Ra before and after O3 exposure prevented development of AHR and decreased BAL fluid neutrophilia. Increases in chemokine levels in lung homogenates, tumor necrosis factor-α, MIP-2, and keratinocyte chemoattractant following O3 exposure were prevented by IL-1Ra. Inhalation of dexamethasone, an inhibitor of IL-1 production, blocked the development of AHR, BAL fluid neutrophilia, and decreased levels of IL-1 following O3 exposure. In summary, acute exposure to O3 induces AHR, neutrophilic inflammation, epithelial damage, and IL-1. An IL-1Ra effectively prevents the development of altered airway function, inflammation, and structural damage.

Original languageEnglish
Pages (from-to)830-836
Number of pages7
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume30
Issue number6
DOIs
Publication statusPublished - 2004 Jun 1

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Park, J. W., Taube, C., Swasey, C., Kodama, T., Joetham, A., Balhorn, A., Takeda, K., Miyahara, N., Allen, C. B., Dakhama, A., Kim, S. H., Dinarello, C. A., & Gelfand, E. W. (2004). Interleukin-1 receptor antagonist attenuates airway hyperresponsiveness following exposure to ozone. American Journal of Respiratory Cell and Molecular Biology, 30(6), 830-836. https://doi.org/10.1165/rcmb.2003-0373OC