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DIILD mouse model

Translational chronic drug-induced ILD mouse model, characterized by low-grade inflammation, fibrosis and dilated large airways

by I Mahmutovic Persson, J Liu, R In 'T Zandt, N Fransén Petterson, A Örbom, H Falk-Håkansson, C Carvalho, K Von Wachenfeldt, L E Olsson

European Respiratory Journal 2022 60: 581 (conference abstract). doi: 10.1183/13993003.congress-2022.581


Many systemically administrated drugs have reportedly shown to cause drug-induced interstitial lung disease (DIILD). Early disease detection is important in order to gain the best treatment outcomes. Here, we aimed to develop non-invasive MRI biomarkers, to allow for assessment of disease progression in a chronic model of bleomycin (BL)-induced ILD.

Methods: C57BL/6 mice received i.p. injections of BL (or Saline as control) 2 d/wk, for 4 wks. MRI (RARE and UTE sequences) was performed in wks 3 and 4, as well as 1-2 wks after final dosing. Lung sections from each group were stained with Masson’s-Trichrome followed by modified Ashcroft scoring.

Results: BL-challenged mice showed increased lung/body weight-ratio (p<0.05) while significant signs of low-grade inflammation and fibrosis (p<0.05) were found by histological analysis, indicating lesions emanating from the vascular side. Fibrosis progression was most apparent during the resting period (4+2wk) (p<0.001). These changes were also visualized by MRI (RARE), with increasing lesion size over time (p<0.05). MRI (UTE) analysis also showed increasing airway diameter during disease progression in the BL group.

Conclusion: With non-invasive MRI we could map the lesions and follow the progression of dilated airways over time. This model is clinically relevant and therefore suitable to use for studying DIILD as well as progressive fibrosis.