title: Attenuated lung fibrosis in interleukin 6 knock-out mice after C-ion irradiation to lung.
abstract: There is a great deal of evidence that a cyclic cascade of inflammatory cytokines, together with the activation of macrophages, is initiated very early after irradiation to develop lung fibrosis in a late phase. To understand the persistent effects of cytokines, the cytokine gene of knock out or transgenic mouse is one of the useful tools. In this study, we evaluated a role of a key molecule, interleukin-6 (IL-6), in the late-phase inflammatory response and subsequent fibrotic changes after irradiation using wild-type (WT) and IL-6 knock out (IL-6 KO) mice. The mice underwent thoracic irradiation with 10 Gy of C-ion beam or sham-irradiation and were examined by histology. Immunoreactivity for IL-6 was induced at the site of bronchiolar epithelium, in pneumocytes and in monocytes by C-ion irradiation. At 24 weeks after irradiation, the infiltration of macrophages, detected by positive immunohistological staining with Mac3 antibody, was observed in alveolar spaces both in WT and IL-6 KO mice. The thickening of bronchiolar and alveolar walls exhibited in WT mice, but not KO mice, and fibrotic changes detected by Masson-Trichrome staining, were observed only in the lungs of WT mice, while it was attenuated in IL-6 KO mice. These results indicated that IL-6 might not be essential for activating macrophages in the late phase, but plays an important role for fibrotic changes of the alveolar wall after irradiation.
authors.affiliation: Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Saito-Fujita
authors.forename: Mayumi
authors.initials: M
authors.lastname: Iwakawa
authors.forename: Etsuko
authors.initials: E
authors.lastname: Nakamura
authors.forename: Miyako
authors.initials: M
authors.lastname: Nakawatari
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Fujita
authors.forename: Takashi
authors.initials: T
authors.lastname: Moritake
authors.forename: Takashi
authors.initials: T
authors.lastname: Imai
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D020450:Heavy Ions; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011829:Radiation Dosage; D017564:Radiation Pneumonitis / Q000378:metabolism* / Q000473:pathology*
chemical_list: D002250:Carbon Radioisotopes; D015850:Interleukin-6