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PMID: 15374841 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Treatment of cockroach allergen asthma model with imatinib attenuates airway responses.

American journal of respiratory and critical care medicine ·Vol. 171 ·No. 1 ·2005-01-01 ·Pages 35-9

Berlin AA, Lukacs NW

Abstract

In the present study it was determined whether a pharmacologic approach to blocking receptor tyrosine kinase-mediated activation during allergic airway responses could be beneficial. To examine these responses, allergic mice were given a single oral dose of imatinib at clinically relevant concentrations, ranging from 0.05 to 50 mg/kg, by oral gavages just before allergen challenge. The reduction in the allergen-induced responses was significant and centered on reducing overall inflammation as well as pulmonary cytokine levels. In particular, the treatment of the mice with imatinib significantly attenuated airway hyperreactivity and peribronchial eosinophil accumulation, and significantly reduced Th2 cytokines, interleukin-4 and interleukin-13. In addition, chemokines previously associated with allergen-induced pulmonary disease, CCL2, CCL5, and CCL6, were significantly reduced in the lungs of the imatinib-treated animals. Together these data demonstrate that the pharmacologic inhibitor imatinib may provide a clinically attractive therapy for allergic, asthmatic responses.

MeSH Terms
Allergens Animals Asthma/drug therapy,immunology,metabolism,pathology,physiopathology Benzamides Bronchi/pathology Bronchial Hyperreactivity Chemokines/metabolism Cockroaches Cytokines/metabolism Eosinophils/pathology Imatinib Mesylate Lung/metabolism Mice Mice, Inbred BALB C Piperazines/therapeutic use Protein-Tyrosine Kinases/antagonists & inhibitors Pyrimidines/therapeutic use
Chemicals
Allergens Benzamides Chemokines Cytokines Piperazines Pyrimidines Imatinib Mesylate Protein-Tyrosine Kinases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Berlin Aaron A
University of Michigan, Pathology, 1301 Catherine St., Ann Arbor, MI 48109-0602, USA.
Lukacs Nicholas W
Article Info
Journal
American journal of respiratory and critical care medicine
Abbr.
Am J Respir Crit Care Med
ISSN
1073-449X
Published
2005-01-01
Epub
2004-00-16
Pages
35-9
Language
English
Region
United States
NLM ID
9421642
Subset
IM
Grants
NIAID NIH HHS · AI36302 · United States
NHLBI NIH HHS · HL58178 · United States
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