IL-10 gene knockout attenuates allergen-induced airway hyperresponsiveness in C57BL/6 mice

J. Paul Justice, Y. Shibata, Sanjiv Sur, J. Mustafa, M. Fan, M. R. Van Scott

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Intratracheal administration of interleukin-10 (IL-10) has been reported to inhibit allergic inflammation but augment airway hyperresponsiveness (AHR). In the present study, airway and smooth muscle responsiveness to methacholine (MCh) were compared in wild-type (WT) and IL-10-deficient (IL-10-KO) mice to investigate the role of endogenous IL-10 in AHR development. Naive WT and IL-10-KO mice exhibited similar dose-dependent increases in airway resistance (Raw) to intravenous MCh. Sensitization and challenge with ragweed (RW) induced a twofold increase in responsiveness to intravenous MCh in WT mice, but hyperresponsiveness was not observed in similarly treated IL-10-KO mice. Likewise, tracheal rings from RW-sensitized and -challenged WT mice exhibited a fourfold greater responsiveness to MCh than IL-10-KO tracheal preparations. Measurements of airway constriction by whole body plethysmography further supported the Raw and tracheal ring data (i.e., AHR was not observed in the absence of IL-10). Interestingly, factors previously implicated in the development of AHR, including IL-4, IL-5, IL-13, IgA, IgG1, IgE, eosinophilia, and lymphocyte recruitment to the airways, were upregulated in the IL-10-KO mice. Treatment with recombinant murine IL-10 at the time of allergen challenge reduced the magnitude of inflammation but reinstated AHR development in IL-10-KO mice. Adoptive transfer of mononuclear splenocytes to IL-10-sufficient severe combined immunodeficient mice indicated that lymphocytes were an important source of the IL-10 impacting AHR development. These results provide evidence that IL-10 expression promotes the development of allergeninduced smooth muscle hyperresponsiveness.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume280
Issue number2 24-2
StatePublished - Feb 2001

Fingerprint

Gene Knockout Techniques
Inbred C57BL Mouse
Interleukin-10
Allergens
Methacholine Chloride
Ambrosia
Smooth Muscle
Whole Body Plethysmography
Lymphocytes
Inflammation
Airway Resistance
SCID Mice
Interleukin-13
Adoptive Transfer
Interleukin-5
Eosinophilia
Constriction
Interleukin-4
Immunoglobulin A
Immunoglobulin E

Keywords

  • Asthma
  • Bronchial hyperresponsiveness
  • Eosinophilia
  • Interleukin-10

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

IL-10 gene knockout attenuates allergen-induced airway hyperresponsiveness in C57BL/6 mice. / Justice, J. Paul; Shibata, Y.; Sur, Sanjiv; Mustafa, J.; Fan, M.; Van Scott, M. R.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 280, No. 2 24-2, 02.2001.

Research output: Contribution to journalArticle

Justice, J. Paul ; Shibata, Y. ; Sur, Sanjiv ; Mustafa, J. ; Fan, M. ; Van Scott, M. R. / IL-10 gene knockout attenuates allergen-induced airway hyperresponsiveness in C57BL/6 mice. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2001 ; Vol. 280, No. 2 24-2.
@article{9833d0741a3244038e7bad9cf1a4e6da,
title = "IL-10 gene knockout attenuates allergen-induced airway hyperresponsiveness in C57BL/6 mice",
abstract = "Intratracheal administration of interleukin-10 (IL-10) has been reported to inhibit allergic inflammation but augment airway hyperresponsiveness (AHR). In the present study, airway and smooth muscle responsiveness to methacholine (MCh) were compared in wild-type (WT) and IL-10-deficient (IL-10-KO) mice to investigate the role of endogenous IL-10 in AHR development. Naive WT and IL-10-KO mice exhibited similar dose-dependent increases in airway resistance (Raw) to intravenous MCh. Sensitization and challenge with ragweed (RW) induced a twofold increase in responsiveness to intravenous MCh in WT mice, but hyperresponsiveness was not observed in similarly treated IL-10-KO mice. Likewise, tracheal rings from RW-sensitized and -challenged WT mice exhibited a fourfold greater responsiveness to MCh than IL-10-KO tracheal preparations. Measurements of airway constriction by whole body plethysmography further supported the Raw and tracheal ring data (i.e., AHR was not observed in the absence of IL-10). Interestingly, factors previously implicated in the development of AHR, including IL-4, IL-5, IL-13, IgA, IgG1, IgE, eosinophilia, and lymphocyte recruitment to the airways, were upregulated in the IL-10-KO mice. Treatment with recombinant murine IL-10 at the time of allergen challenge reduced the magnitude of inflammation but reinstated AHR development in IL-10-KO mice. Adoptive transfer of mononuclear splenocytes to IL-10-sufficient severe combined immunodeficient mice indicated that lymphocytes were an important source of the IL-10 impacting AHR development. These results provide evidence that IL-10 expression promotes the development of allergeninduced smooth muscle hyperresponsiveness.",
keywords = "Asthma, Bronchial hyperresponsiveness, Eosinophilia, Interleukin-10",
author = "Justice, {J. Paul} and Y. Shibata and Sanjiv Sur and J. Mustafa and M. Fan and {Van Scott}, {M. R.}",
year = "2001",
month = "2",
language = "English (US)",
volume = "280",
journal = "American Journal of Physiology - Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "2 24-2",

}

TY - JOUR

T1 - IL-10 gene knockout attenuates allergen-induced airway hyperresponsiveness in C57BL/6 mice

AU - Justice, J. Paul

AU - Shibata, Y.

AU - Sur, Sanjiv

AU - Mustafa, J.

AU - Fan, M.

AU - Van Scott, M. R.

PY - 2001/2

Y1 - 2001/2

N2 - Intratracheal administration of interleukin-10 (IL-10) has been reported to inhibit allergic inflammation but augment airway hyperresponsiveness (AHR). In the present study, airway and smooth muscle responsiveness to methacholine (MCh) were compared in wild-type (WT) and IL-10-deficient (IL-10-KO) mice to investigate the role of endogenous IL-10 in AHR development. Naive WT and IL-10-KO mice exhibited similar dose-dependent increases in airway resistance (Raw) to intravenous MCh. Sensitization and challenge with ragweed (RW) induced a twofold increase in responsiveness to intravenous MCh in WT mice, but hyperresponsiveness was not observed in similarly treated IL-10-KO mice. Likewise, tracheal rings from RW-sensitized and -challenged WT mice exhibited a fourfold greater responsiveness to MCh than IL-10-KO tracheal preparations. Measurements of airway constriction by whole body plethysmography further supported the Raw and tracheal ring data (i.e., AHR was not observed in the absence of IL-10). Interestingly, factors previously implicated in the development of AHR, including IL-4, IL-5, IL-13, IgA, IgG1, IgE, eosinophilia, and lymphocyte recruitment to the airways, were upregulated in the IL-10-KO mice. Treatment with recombinant murine IL-10 at the time of allergen challenge reduced the magnitude of inflammation but reinstated AHR development in IL-10-KO mice. Adoptive transfer of mononuclear splenocytes to IL-10-sufficient severe combined immunodeficient mice indicated that lymphocytes were an important source of the IL-10 impacting AHR development. These results provide evidence that IL-10 expression promotes the development of allergeninduced smooth muscle hyperresponsiveness.

AB - Intratracheal administration of interleukin-10 (IL-10) has been reported to inhibit allergic inflammation but augment airway hyperresponsiveness (AHR). In the present study, airway and smooth muscle responsiveness to methacholine (MCh) were compared in wild-type (WT) and IL-10-deficient (IL-10-KO) mice to investigate the role of endogenous IL-10 in AHR development. Naive WT and IL-10-KO mice exhibited similar dose-dependent increases in airway resistance (Raw) to intravenous MCh. Sensitization and challenge with ragweed (RW) induced a twofold increase in responsiveness to intravenous MCh in WT mice, but hyperresponsiveness was not observed in similarly treated IL-10-KO mice. Likewise, tracheal rings from RW-sensitized and -challenged WT mice exhibited a fourfold greater responsiveness to MCh than IL-10-KO tracheal preparations. Measurements of airway constriction by whole body plethysmography further supported the Raw and tracheal ring data (i.e., AHR was not observed in the absence of IL-10). Interestingly, factors previously implicated in the development of AHR, including IL-4, IL-5, IL-13, IgA, IgG1, IgE, eosinophilia, and lymphocyte recruitment to the airways, were upregulated in the IL-10-KO mice. Treatment with recombinant murine IL-10 at the time of allergen challenge reduced the magnitude of inflammation but reinstated AHR development in IL-10-KO mice. Adoptive transfer of mononuclear splenocytes to IL-10-sufficient severe combined immunodeficient mice indicated that lymphocytes were an important source of the IL-10 impacting AHR development. These results provide evidence that IL-10 expression promotes the development of allergeninduced smooth muscle hyperresponsiveness.

KW - Asthma

KW - Bronchial hyperresponsiveness

KW - Eosinophilia

KW - Interleukin-10

UR - http://www.scopus.com/inward/record.url?scp=0035012780&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035012780&partnerID=8YFLogxK

M3 - Article

VL - 280

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 2 24-2

ER -