Imatinib therapy reduces radiation-induced pulmonary mast cell influx and delays lung disease in the mouse.
OBJECTIVE
Radiotherapy can induce the inflammatory response of alveolitis and the excessive repair response of fibrosis through incompletely defined mechanisms. In previous murine studies we showed the alveolitis response to thoracic irradiation to correlate with pulmonary mast cell numbers and fibrosis severity to partially depend on the extent of alveolitis. Herein we investigate whether the mast cell blocker imatinib reduces the alveolitis and/or fibrosis response to irradiation.


METHODS
Mice of three strains received 18 Gy whole thorax irradiation and a subset of these were treated with imatinib (100 mg/kg) daily from the day of irradiation until euthanasia due to the presentation of distress symptoms.


RESULTS
Imatinib treatment increased the post irradiation survival time of the mice by an average of 23% and significantly reduced the pulmonary mast cell influx. The alveolitis and fibrosis phenotypes, evident histologically, were not altered by imatinib treatment in mice euthanised upon presentation of respiratory distress. The imatinib treated mice did, however, have less disease than did mice receiving radiation alone, when both groups were assessed at a common time point.


CONCLUSIONS
We conclude that imatinib treatment reduces radiation-induced mast cell influx into the lungs and delays the alveolitis or fibrosis response of mice.
Thomas
David M
DM
Department of Medicine, McGill University, Montreal, Quebec, Canada.
Fox
Jessica
J
Haston
Christina K
CK
D000818:Animals; D001549:Benzamides; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D000068877:Imatinib Mesylate; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D008171:Lung Diseases / Q000276:immunology / Q000517:prevention & control*; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000276:immunology* / Q000378:metabolism
D001549:Benzamides; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D011743:Pyrimidines; D000068877:Imatinib Mesylate