Airway hyperresponsiveness

A story of mice and men and cytokines

Robert G. Townley, Masahide Horiba

Research output: Contribution to journalReview article

45 Citations (Scopus)

Abstract

Bronchial hyperresponsiveness (BHR) is an essential part of the definition of asthma. Although our understanding of the allergic inflammatory and immunologic mechanisms of asthma have markedly increased, the mechanism of BHR remains to be elucidated. Increased BHR is associated temporally with exposure to allergens, certain respiratory viruses, pollutants such as ozone, and certain occupational chemicals. An important research use of determining the degree of BHR to direct and indirect challenge is to determine the efficacy of pharmacologic and immunodulatory agents. Beta-adrenergic agents inhibit BHR and certain genetic polymorphisms of the beta-adrenergic receptor are associated with increased BHR. When β-adrenergic receptors are blocked, sensitivity to allergens is markedly increased in patients with asthma and animal models of asthma. Allergen challenge and clinical asthma are associated with synthesis and release of pro-inflammatory cytokines such as IL-1 and TNF-α which have been shown to decrease the response to β-agonists and increased the reactivity to methacholine and the airways neutrophils and alveolar macrophages. The Th2 cytokine IL-13 is increased in the airways of asthmatics and increases BHR in normal unsensitized animals. The mechanisms of this effect of IL-13 are being intensively investigated. Our group has shown that IL-13 induced BHR persisted for at least 7 days and the soluble receptor IL-13R2α protected against their BHR. Other investigators have demonstrated that IL-13 is necessary and sufficient for the induction of BHR and that eosinophilic airway inflammation in the absence of IL-13 fails to induce BHR. These studies indicate that treatment of human asthma with antagonists of IL-13 may be very effective.

Original languageEnglish
Pages (from-to)85-109
Number of pages25
JournalClinical Reviews in Allergy and Immunology
Volume24
Issue number1
DOIs
StatePublished - Feb 2003

Fingerprint

Interleukin-13
Asthma
Cytokines
Allergens
Methacholine Chloride
Ozone
Receptors, Adrenergic, beta
Alveolar Macrophages
Genetic Polymorphisms
Interleukin-1
Adrenergic Agents
Adrenergic Receptors
Neutrophils
Animal Models
Research Personnel
Viruses
Inflammation
Research

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy

Cite this

Airway hyperresponsiveness : A story of mice and men and cytokines. / Townley, Robert G.; Horiba, Masahide.

In: Clinical Reviews in Allergy and Immunology, Vol. 24, No. 1, 02.2003, p. 85-109.

Research output: Contribution to journalReview article

Townley, Robert G. ; Horiba, Masahide. / Airway hyperresponsiveness : A story of mice and men and cytokines. In: Clinical Reviews in Allergy and Immunology. 2003 ; Vol. 24, No. 1. pp. 85-109.
@article{372f28df0fbe44578e8c85a95e98e043,
title = "Airway hyperresponsiveness: A story of mice and men and cytokines",
abstract = "Bronchial hyperresponsiveness (BHR) is an essential part of the definition of asthma. Although our understanding of the allergic inflammatory and immunologic mechanisms of asthma have markedly increased, the mechanism of BHR remains to be elucidated. Increased BHR is associated temporally with exposure to allergens, certain respiratory viruses, pollutants such as ozone, and certain occupational chemicals. An important research use of determining the degree of BHR to direct and indirect challenge is to determine the efficacy of pharmacologic and immunodulatory agents. Beta-adrenergic agents inhibit BHR and certain genetic polymorphisms of the beta-adrenergic receptor are associated with increased BHR. When β-adrenergic receptors are blocked, sensitivity to allergens is markedly increased in patients with asthma and animal models of asthma. Allergen challenge and clinical asthma are associated with synthesis and release of pro-inflammatory cytokines such as IL-1 and TNF-α which have been shown to decrease the response to β-agonists and increased the reactivity to methacholine and the airways neutrophils and alveolar macrophages. The Th2 cytokine IL-13 is increased in the airways of asthmatics and increases BHR in normal unsensitized animals. The mechanisms of this effect of IL-13 are being intensively investigated. Our group has shown that IL-13 induced BHR persisted for at least 7 days and the soluble receptor IL-13R2α protected against their BHR. Other investigators have demonstrated that IL-13 is necessary and sufficient for the induction of BHR and that eosinophilic airway inflammation in the absence of IL-13 fails to induce BHR. These studies indicate that treatment of human asthma with antagonists of IL-13 may be very effective.",
author = "Townley, {Robert G.} and Masahide Horiba",
year = "2003",
month = "2",
doi = "10.1385/CRIAI:24:1:85",
language = "English",
volume = "24",
pages = "85--109",
journal = "Clinical Reviews in Allergy and Immunology",
issn = "1080-0549",
publisher = "Humana Press",
number = "1",

}

TY - JOUR

T1 - Airway hyperresponsiveness

T2 - A story of mice and men and cytokines

AU - Townley, Robert G.

AU - Horiba, Masahide

PY - 2003/2

Y1 - 2003/2

N2 - Bronchial hyperresponsiveness (BHR) is an essential part of the definition of asthma. Although our understanding of the allergic inflammatory and immunologic mechanisms of asthma have markedly increased, the mechanism of BHR remains to be elucidated. Increased BHR is associated temporally with exposure to allergens, certain respiratory viruses, pollutants such as ozone, and certain occupational chemicals. An important research use of determining the degree of BHR to direct and indirect challenge is to determine the efficacy of pharmacologic and immunodulatory agents. Beta-adrenergic agents inhibit BHR and certain genetic polymorphisms of the beta-adrenergic receptor are associated with increased BHR. When β-adrenergic receptors are blocked, sensitivity to allergens is markedly increased in patients with asthma and animal models of asthma. Allergen challenge and clinical asthma are associated with synthesis and release of pro-inflammatory cytokines such as IL-1 and TNF-α which have been shown to decrease the response to β-agonists and increased the reactivity to methacholine and the airways neutrophils and alveolar macrophages. The Th2 cytokine IL-13 is increased in the airways of asthmatics and increases BHR in normal unsensitized animals. The mechanisms of this effect of IL-13 are being intensively investigated. Our group has shown that IL-13 induced BHR persisted for at least 7 days and the soluble receptor IL-13R2α protected against their BHR. Other investigators have demonstrated that IL-13 is necessary and sufficient for the induction of BHR and that eosinophilic airway inflammation in the absence of IL-13 fails to induce BHR. These studies indicate that treatment of human asthma with antagonists of IL-13 may be very effective.

AB - Bronchial hyperresponsiveness (BHR) is an essential part of the definition of asthma. Although our understanding of the allergic inflammatory and immunologic mechanisms of asthma have markedly increased, the mechanism of BHR remains to be elucidated. Increased BHR is associated temporally with exposure to allergens, certain respiratory viruses, pollutants such as ozone, and certain occupational chemicals. An important research use of determining the degree of BHR to direct and indirect challenge is to determine the efficacy of pharmacologic and immunodulatory agents. Beta-adrenergic agents inhibit BHR and certain genetic polymorphisms of the beta-adrenergic receptor are associated with increased BHR. When β-adrenergic receptors are blocked, sensitivity to allergens is markedly increased in patients with asthma and animal models of asthma. Allergen challenge and clinical asthma are associated with synthesis and release of pro-inflammatory cytokines such as IL-1 and TNF-α which have been shown to decrease the response to β-agonists and increased the reactivity to methacholine and the airways neutrophils and alveolar macrophages. The Th2 cytokine IL-13 is increased in the airways of asthmatics and increases BHR in normal unsensitized animals. The mechanisms of this effect of IL-13 are being intensively investigated. Our group has shown that IL-13 induced BHR persisted for at least 7 days and the soluble receptor IL-13R2α protected against their BHR. Other investigators have demonstrated that IL-13 is necessary and sufficient for the induction of BHR and that eosinophilic airway inflammation in the absence of IL-13 fails to induce BHR. These studies indicate that treatment of human asthma with antagonists of IL-13 may be very effective.

UR - http://www.scopus.com/inward/record.url?scp=0037296809&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037296809&partnerID=8YFLogxK

U2 - 10.1385/CRIAI:24:1:85

DO - 10.1385/CRIAI:24:1:85

M3 - Review article

VL - 24

SP - 85

EP - 109

JO - Clinical Reviews in Allergy and Immunology

JF - Clinical Reviews in Allergy and Immunology

SN - 1080-0549

IS - 1

ER -