Published ahead of print on January 23, 2004, doi:10.1165/rcmb.2003-0395OC
© 2004 American Thoracic Society DOI: 10.1165/rcmb.2003-0395OC Inhibition of Early Airway Neutrophilia Does Not Affect Development of Airway HyperresponsivenessDivision of Cell Biology, Department of Pediatrics, and Department of Medicine, National Jewish Medical and Research Center, Denver; Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado; and Charité Humanmedizin Berlin, Campus Benjamin Franklin, Medical Department I, Berlin, Germany Address correspondence to: Erwin W. Gelfand, M.D., National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail: gelfande{at}njc.org
The effect of modifying early neutrophil-mediated inflammation on the development of airway hyperresponsiveness (AHR) was investigated using an interleukin (IL)-1 receptor antagonist (IL-1Ra), an anti–IL-18 antibody (anti–IL-18) or a p38 mitogen-activated protein kinase (MAPK) inhibitor (M39). Balb/c mice were sensitized to ovalbumin (OVA) and challenged with a single intranasal dose of OVA. Treatment with the IL-1Ra or anti–IL-18 was initiated 20 min before challenge, whereas M39 was administered 4 h before the challenge. Eight hours after challenge, sensitized mice showed significantly higher numbers of neutrophils in bronchoalveolar lavage (BAL) fluid; treatment with IL-1Ra, anti–IL-18, or M39 significantly decreased the influx of neutrophils. At 48 h, none of the treatments affected eosinophil inflammation in BAL fluid and lung tissue, goblet cell hyperplasia, or cytokine levels (IL-4, IL-5, IL-12, IL-13, interferon-
Abbreviations: airway hyperresponsiveness, AHR • bronchoalveolar lavage, BAL • dynamic compliance, Cdyn • enzyme-linked immunosorbent assay, ELISA • immunoglobulin, Ig • interleukin, IL • lipopolysaccharide, LPS • mitogen-activated protein kinase, MAPK • major basic protein, MBP • methacholine, MCh • macrophage inflammatory protein, MIP • ovalbumin, OVA • periodic acid Schiff, PAS • lung resistance, RL • single intranasal challenge, sin • tumor necrosis factor, TNF This article has been cited by other articles:
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) in BAL fluid. Anti–IL-18 or IL-1Ra had no effect on the development of AHR, whereas M39-treated mice showed a decrease in methacholine responsiveness. These results demonstrate that early neutrophil influx following allergen challenge is mediated by IL-1, IL-18, and p38 MAPK. However, neutralization of IL-1 and IL-18 did not affect the later development of AHR and eosinophilic airway inflammation. The effects of inhibiting p38 MAPK in decreasing AHR indicate activities independent of its prevention of neutrophil accumulation. 
