title: Epidermal growth factor receptor-tyrosine kinase inhibitor (gefitinib) augments pneumonitis, but attenuates lung fibrosis in response to radiation injury in rats.
abstract: BACKGROUND
  Gefitinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, has been reported to be associated with interstitial lung disorders, and their high incidence and mortality have become a matter of great concern, especially in Japan. In this study, we investigated the effect of gefitinib on different phases of radiation-induced lung disorders in an experimental model.
  
  
  METHODS
  The thoraxes of Wistar rats were irradiated on day 1 with a single X-ray dose of 20 Gy, and gefitinib (50 mg/kg/day) was orally administered from day 1 to 14. The rat lungs were harvested on days 15 and 57 and the bronchoalveolar lavage (BAL) was performed.
  
  
  RESULTS
  Gefitinib treatment increased the infiltration of inflammatory cells, which produced more pro-inflammatory cytokines (IL-6, IL-1β), in the lungs of the irradiated rats on days 15 and 57, while gefitinib treatment reduced collagen content of the lungs in irradiated rats and decreased proliferation and EGFR expression in the lung fibroblasts from irradiated rats on day 57.
  
  
  CONCLUSIONS
  In irradiated rats, gefitinib treatment augmented lung inflammation, including inflammatory cell infiltration and pro-inflammatory cytokine expression, while gefitinib treatment attenuated fibrotic lung remodeling due to the inhibition of lung fibroblast proliferation.
authors.affiliation: Department of Respiratory Medicine and Rheumatology, the University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Miyake
authors.forename: Kenji
authors.initials: K
authors.lastname: Tani
authors.forename: Soji
authors.initials: S
authors.lastname: Kakiuchi
authors.forename: Chiyuki
authors.initials: C
authors.lastname: Suzuka
authors.forename: Yuko
authors.initials: Y
authors.lastname: Toyoda
authors.forename: Jun
authors.initials: J
authors.lastname: Kishi
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tezuka
authors.forename: Shino
authors.initials: S
authors.lastname: Yuasa
authors.forename: Masaki
authors.initials: M
authors.lastname: Hanibuchi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Aono
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Nishioka
authors.forename: Saburo
authors.initials: S
authors.lastname: Sone
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000077156:Gefitinib; D008297:Male; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000473:pathology*; D011799:Quinazolines / Q000494:pharmacology*; D017564:Radiation Pneumonitis / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib