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Published ahead of print on January 30, 2004, doi:10.1165/rcmb.2003-0373OC

Am. J. Respir. Cell Mol. Biol., Volume 30, Number 6, June 2004, 830-836

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Submitted on October 17, 2003
Revised on January 21, 2004

IL-1 Receptor Antagonist Attenuates Airway Hyperresponsiveness Following Exposure to Ozone

Jung-Won Park1, Christian Taube1, Christina Swasey1, Taku Kodama1, Anthony Joetham1, Annette Balhorn1, Katsuyuki Takeda1, Nobuaki Miyahara1, Corrie B Allen1, Azzeddine Dakhama1, Soo-Hyun Kim2, Charles A Dinarello2, and Erwin W Gelfand1*

1 Pediatrics, National Jewish Center, Denver, CO, USA, 2 Medicine, University of Colorado Health Sciences Center, Denver, CO, USA

* To whom correspondence should be addressed. E-mail: gelfande{at}njc.org.

The role of an IL-1 receptor antagonist (IL-1Ra) on the development of AHR and airway inflammation following acute O3 exposure in mice. Exposure of C57/BL6 mice to O3 at a concentration of 2.0 parts per million (ppm) or filtered air for 3 hrs resulted in increases in airway responsiveness to inhaled methacholine (MCh), 8 and 16 hrs after the exposure, and an increase in neutrophils in the bronchoalveolar lavage (BAL) fluid. IL-1{beta} expression, assessed by gene microarray, was increased 2-fold 4 hrs after O3 exposure and returned to baseline levels by 24 hrs. Levels of IL-1{beta} in lung homogenates were also increased 8 hrs following O3 exposure. Administration of (human) IL-1Ra prior to and following O3 exposure prevented development of AHR and decreased BAL fluid neutrophilia. Increases in chemokine levels in lung homogenates, TNF-{alpha}, MIP-2 and KC, 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.




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