Development of translational ILDmodels:How drug-induced side effects trigger alterations in the lung tissue upon systemical long-term exposure?

Drug-induced interstitial lung disease (DIILD) is highly underdiagnosed and very few preclinical models exist to study these event. To address the increasing issue of drug-induced toxicity, we aimed to develop two translational models in rats using two different drugs; Bleomycin (BL) or Nitrofurantoin (NF). Here long-term systemic exposure to medication was applied to mimic clinical features. Methods: Sprague-Dawley rats received BL or NF challenge subcutaneously, 3 days/week during 1-4 weeks. MRI was performed at week 5. At termination (week 1, 2, 3, 4 and 5), BAL was collected and analysed for total protein and inflammatory cells. Lungs were further analysed by histology. Results: The two models showed diverse pathological alteration in the lungs (Figure). BL rats presented weight loss and significant increase (p Conclusion: Here we present two DIILD models in rat, with distinct pathological changes over time showing two examples of alterations in the lung upon medication. These models serve as platforms for further biomarker development in DIILD.