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Inhibition of early airway neutrophilia does not affect development of airway hyperresponsiveness.
Am J Respir Cell Mol Biol 2004; 30(6):837-43AJ

Abstract

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-gamma) 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.

Authors+Show Affiliations

Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14742296

Citation

Taube, Christian, et al. "Inhibition of Early Airway Neutrophilia Does Not Affect Development of Airway Hyperresponsiveness." American Journal of Respiratory Cell and Molecular Biology, vol. 30, no. 6, 2004, pp. 837-43.
Taube C, Nick JA, Siegmund B, et al. Inhibition of early airway neutrophilia does not affect development of airway hyperresponsiveness. Am J Respir Cell Mol Biol. 2004;30(6):837-43.
Taube, C., Nick, J. A., Siegmund, B., Duez, C., Takeda, K., Rha, Y. H., ... Gelfand, E. W. (2004). Inhibition of early airway neutrophilia does not affect development of airway hyperresponsiveness. American Journal of Respiratory Cell and Molecular Biology, 30(6), pp. 837-43.
Taube C, et al. Inhibition of Early Airway Neutrophilia Does Not Affect Development of Airway Hyperresponsiveness. Am J Respir Cell Mol Biol. 2004;30(6):837-43. PubMed PMID: 14742296.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of early airway neutrophilia does not affect development of airway hyperresponsiveness. AU - Taube,Christian, AU - Nick,Jerry A, AU - Siegmund,Britta, AU - Duez,Catherine, AU - Takeda,Katsuyuki, AU - Rha,Yeong-Ho, AU - Park,Jung-Won, AU - Joetham,Anthony, AU - Poch,Katie, AU - Dakhama,Azzeddine, AU - Dinarello,Charles A, AU - Gelfand,Erwin W, Y1 - 2004/01/23/ PY - 2004/1/27/pubmed PY - 2004/6/30/medline PY - 2004/1/27/entrez SP - 837 EP - 43 JF - American journal of respiratory cell and molecular biology JO - Am. J. Respir. Cell Mol. Biol. VL - 30 IS - 6 N2 - 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-gamma) 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. SN - 1044-1549 UR - https://www.unboundmedicine.com/medline/citation/14742296/Inhibition_of_early_airway_neutrophilia_does_not_affect_development_of_airway_hyperresponsiveness_ L2 - http://www.atsjournals.org/doi/full/10.1165/rcmb.2003-0395OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -