Treatment of cockroach allergen asthma model with imatinib attenuates airway responses.
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.
Berlin
Aaron A
AA
University of Michigan, Pathology, 1301 Catherine St., Ann Arbor, MI 48109-0602, USA.
Lukacs
Nicholas W
NW
D000485:Allergens; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001549:Benzamides; D001980:Bronchi / Q000473:pathology; D016535:Bronchial Hyperreactivity; D018925:Chemokines / Q000378:metabolism; D003058:Cockroaches; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000473:pathology; D000068877:Imatinib Mesylate; D008168:Lung / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010879:Piperazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000627:therapeutic use*
D000485:Allergens; D001549:Benzamides; D018925:Chemokines; D016207:Cytokines; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases