TY - JOUR
T1 - Interleukin-1 receptor antagonist attenuates airway hyperresponsiveness following exposure to ozone
AU - Park, Jung Won
AU - Taube, Christian
AU - Swasey, Christina
AU - Kodama, Taku
AU - Joetham, Anthony
AU - Balhorn, Annette
AU - Takeda, Katsuyuki
AU - Miyahara, Nobuaki
AU - Allen, Corrie B.
AU - Dakhama, Azzeddine
AU - Kim, Soo Hyun
AU - Dinarello, Charles A.
AU - Gelfand, Erwin W.
PY - 2004/6
Y1 - 2004/6
N2 - 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.
AB - 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.
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U2 - 10.1165/rcmb.2003-0373OC
DO - 10.1165/rcmb.2003-0373OC
M3 - Article
C2 - 14754758
AN - SCOPUS:2942511588
SN - 1044-1549
VL - 30
SP - 830
EP - 836
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
IS - 6
ER -