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

Park, JW; Taube, C; Swasey, C; Kodama, T; Joetham, A; Balhorn, A; Takeda, K; Miyahara, N; Allen, CB; Dakhama, A; Kim, SH; Dinarello, CA; Gelfand, EW

HERO ID

644864

Reference Type

Journal Article

Year

2004

Language

English

PMID

14754758

HERO ID 644864
In Press No
Year 2004
Title Interleukin-1 receptor antagonist attenuates airway hyperresponsiveness following exposure to ozone
Authors Park, JW; Taube, C; Swasey, C; Kodama, T; Joetham, A; Balhorn, A; Takeda, K; Miyahara, N; Allen, CB; Dakhama, A; Kim, SH; Dinarello, CA; Gelfand, EW
Journal American Journal of Respiratory Cell and Molecular Biology
Volume 30
Issue 6
Page Numbers 830-836
Abstract The role of an interleukin (IL)-1 receptor antagonist (IL-1Ra) on the development of airway hyperresponsiveness (AHR) and airway inflammation following acute O(3) exposure in mice was investigated. Exposure of C57/BL6 mice to O(3) 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-1beta expression, assessed by gene microarray, was increased 2-fold 4 h after O(3) exposure, and returned to baseline levels by 24 h. Levels of IL-1beta in lung homogenates were also increased 8 h after O(3) exposure. Administration of (human) IL-1Ra before and after O(3) exposure prevented development of AHR and decreased BAL fluid neutrophilia. Increases in chemokine levels in lung homogenates, tumor necrosis factor-alpha, MIP-2, and keratinocyte chemoattractant following O(3) 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 O(3) exposure. In summary, acute exposure to O(3) induces AHR, neutrophilic inflammation, epithelial damage, and IL-1. An IL-1Ra effectively prevents the development of altered airway function, inflammation, and structural damage.
Doi 10.1165/rcmb.2003-0373OC
Pmid 14754758
Wosid WOS:000221835100010
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English
Is Qa No