IL-10 is necessary for the expression of airway hyperresponsiveness but not pulmonary inflammation after allergic sensitization

IL-10 is necessary for the expression of airway hyperresponsiveness but not pulmonary inflammation after allergic sensitization

Departments of ^*Pediatrics and ^†Medicine, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206; and ^‡Department of Molecular Medicine, McMaster University, Hamilton, ON, Canada L8N 3Z5

Communicated by Philippa Marrack, National Jewish Medical and Research Center, Denver, CO (received for review January 18, 2000)

Abstract

Cytokines play an important role in modulating inflammatory responses and, as a result, airway tone. IL-10 is a regulatory cytokine that has been suggested for treatment of asthma because of its immunosuppressive and anti-inflammatory properties. In contrast to these suggestions, we demonstrate in a model of allergic sensitization that mice deficient in IL-10 (IL-10−/−) develop a pulmonary inflammatory response but fail to exhibit airway hyperresponsiveness in both in vitro and in vivo assessments of lung function. Reconstitution of these deficient mice with the IL-10 gene fully restores development of airway hyperresponsiveness comparable to control mice. These results identify an important role of IL-10, downstream of the inflammatory cascade, in regulating the tone of the airways after allergic sensitization and challenge.

Footnotes

↵ § To whom reprint requests should be addressed. E-mail: gelfande{at}njc.org.
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.100118997.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.100118997
Abbreviations:

Ad/C,

adenovirus control;

Ad/IL-10,

adenovirus/IL-10;

AHR,

airway hyperresponsiveness;

BAL,

bronchoalveolar lavage;

BALF,

BAL fluid;

Cdyn,

dynamic compliance;

EFS,

electrical field stimulation;

EIA,

enzyme immunoassay;

EPO,

eosinophil peroxidase;

LTC4,

leukotriene C4;

MCh,

methacholine;

OVA,

ovalbumin;

PAS,

periodic acid Schiff;

RL,

lung resistance;

Th,

T helper;

WT,

wild type