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

Allergy and Immunology Section, and Pulmonary and Critical Care Section, Department of Medicine, University of Wisconsin, Madison, Wisconsin

Correspondence and requests for reprints should be addressed to Elizabeth A. (Becky) Kelly, Ph.D., Section of Pulmonary and Critical Care Medicine, 600 Highland Avenue, CSC K4/928, University of Wisconsin School of Medicine, Madison, WI 53792-9988. E-mail: eak{at}medicine.wisc.edu

Allergen-induced asthma is characterized by airway eosinophilia and recruitment of helper T (Th) Type 2 lymphocytes. We hypothesized that lymphocyte-associated chemokines contribute to allergen-induced airway inflammation. Sixteen subjects with asthma 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 Th1 and Th2 chemokines and cytokines. Airway cells, cytokines, and lymphocyte-associated chemokines increased after segmental challenge. Th2 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 Th2 and Th1 (monokine-induced by IFN-, IFN-–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 Th2 and Th1 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 after allergen exposure.

Key Words: bronchoalveolar lavage • chemokines • eosinophils • late-phase response • helper T Type 1/helper T Type 2 cells

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