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Published ahead of print on March 4, 2004, doi:10.1164/rccm.200312-1659OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 10, May 2004, 1118-1124

A more recent version of this article appeared on May 15, 2004
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Submitted on December 5, 2003
Accepted on March 3, 2004

Enhanced Generation of T Helper 1- and 2-type Chemokines in Allergen-induced Asthma

Linying Liu1, Nizar N Jarjour2, William W Busse1, and Elizabeth A. B. Kelly2*

1 Department of Medicine, Allergy and Immunology Section, University of Wisconsin, Madison, WI, USA, 2 Department of Medicine, Pulmonary and Critical Care Section, University of Wisconsin, Madison, WI, USA

* To whom correspondence should be addressed. E-mail: eak{at}medicine.wisc.edu.

Allergen-induced asthma is characterized by airway eosinophilia and recruitment of T helper 2-type lymphocytes. We hypothesized that lymphocyte-associated chemokines contribute to allergen-induced airway inflammation. Sixteen asthma subjects were phenotyped according to their response to inhaled antigen as single- or dual-phase responders, and then underwent bronchoscopy and segmental allergen bronchoprovocation. Bronchoalveolar lavage fluids were obtained before and 48 hours after segmental challenge with allergen to determine the cellular response and patterns of T helper 1- and 2-type chemokines and cytokines. Airway cells, cytokines, and lymphocyte-associated chemokines increased after segmental challenge. T helper 2-type chemokines (thymus and activation-regulated chemokine, macrophage-derived chemokine) correlated with airway eosinophils and concentrations of interleukin-5 and -13. In contrast, airway lymphocytes correlated with both type-2 and type-1 (monokine-induced by interferon-{gamma}, interferon-{gamma} inducible protein-10) chemokines. Notably, when subjects were analyzed according to the presence of a late-phase response, concentrations of both types of lymphocyte-associated chemokines were significantly greater in subjects with a dual-response phenotype. Our findings suggest that both T helper 2- and T helper 1-type chemokines may be involved in allergen-induced airway inflammation. However, asthma subjects with a dual-responder phenotype have greater generation of chemokines that may lead to enhanced airway inflammation and obstruction following allergen exposure.
Key words: chemokines, Th1/Th2 cells, eosinophils, late phase response, bronchoalveolar lavage




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