Abstract
The effectiveness of ulinastatin and methylprednisolone in treating pathological changes in mice with radiation-induced lung injury (RILI) was evaluated. Forty C57BL/6 female mice received whole-chest radiation (1.5 Gy/min for 12 min) and were randomly allocated into Group R (single radiation, n = 10), Group U (ulinastatin treatment, n = 10), Group M (methylprednisolone treatment, n = 10), or Group UM (ulinastatin and methylprednisolone treatment, n = 10). Another 10 untreated mice served as controls (Group C). Pathological changes in lung tissue, pulmonary interstitial area density (PIAD) and expression levels of transforming growth factor β1 (TGF-β1) and tumor necrosis factor α (TNF-α) in lung tissue, serum and bronchoalveolar lavage fluid were determined. Alleviation of pathological changes in lung tissue was observed in Groups U, M and UM. Treatment with ulinastatin, methylprednisolone or both effectively delayed the development of fibrosis at 12 weeks after radiation. Ulinastatin, methylprednisolone or both could alleviate the radiation-induced increase in the PIAD (P < 0.05 or P < 0.01). Treatment with ulinastatin, methylprednisolone or both significantly reduced the expression of TNF-α, but not TGF-β1, at 9 weeks after radiation compared with Group R (P < 0.01). Ulinastatin and/or methylprednisolone effectively decreased the level of TNF-α in lung tissue after RILI and inhibited both the inflammatory response and the development of fibrosis.
Highlights
Radiation-induced lung injury (RILI) is a common and severe complication in patients undergoing thoracic radiotherapy, receiving bone marrow transplantation, or involved in nuclear accidents [1,2,3]
507 pulmonary capillary expansion, and hyperemia and inflammatory infiltration foci were observed 2 weeks after radiation in Group R (Fig. 1B). Alleviation of these pathological changes was observed in Groups U, M and UM, suggesting that ulinastatin and methylprednisolone had protective effects during the early phase after radiation exposure (Fig. 1C–E)
Methylprednisolone or both effectively delayed the development of fibrosis and inhibited the infiltration of inflammatory cells (Fig. 2C–E)
Summary
Radiation-induced lung injury (RILI) is a common and severe complication in patients undergoing thoracic radiotherapy, receiving bone marrow transplantation, or involved in nuclear accidents [1,2,3]. Its damage to normal tissue is seen increasingly with the ever more widespread application of radiotherapy for the treatment of tumors. The early phase after acute lung damage is characterized by exudative inflammation complicated by interstitial pneumonia 6–12 weeks after exposure. A later phase is characterized by chronic inflammation, tissue remodeling, and pulmonary fibrosis [5]. Inflammatory cytokines, including transforming growth factor β1 (TGF-β1) and tumor necrosis factor α (TNF-α), play critical roles in regulating the RILI process [6]. TNF-α is involved in the initiation and amplification of the inflammatory responses during RILI [7], and TGF-β1 mediates the proliferation and differentiation of fibroblasts into myofibroblasts, which play a critical role in the fibrotic process via the production of collagen and other extracellular matrix proteins [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
