Attenuated lung fibrosis in interleukin 6 knock-out miceafter C-ion irradiation to lung

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.