Longitudinal MRI and inflammation infiltrates reveal progressive fibrosis compared to resolving wound healing: comparing lung injury models of Bleomycin and LPS

The wound healing process in acute lung injury is frequently studied, yet the question remains; why does acute inflammation resolve after certain injury exposure and other times fibrosis and scaring of the lung tissue develops? We employed two lung injury models; bleomycin (BL) and the LPS model to study the injury resolution. <bold>Methods:</bold> Sprague-Dawley male rats received i.t. instillation of either BL (1000iU), LPS (5mg/kg) or Saline (control). Radial MRI with two echo-times (TE=1ms, 0.324ms) was performed days after instillation, as well as 4 weeks after dosing. At termination, lungs were assessed by Masson’s Trichrome staining, flow cytometry cell sorting and BAL cell evaluation. <bold>Results:</bold> Both injury groups showed significantly increased signal (p<0.05) on the MRI_LONG-TE (oedema signal) days after instillation compared to controls. BL-challenged rats showed significant (p<0.05) fibrotic progression over 4 weeks shown by MRI_SHORT-TE (tissue signal) in comparison to controls, while the LPS-challenged rats recovered and resolved the injury without fibrosis progression. Both injury groups had increased lung volume and pronounced inflammation although BL-exposed rats had mixed leukocyte infiltrates with significantly (p<0.01) higher eosinophil counts vs. LPS-exposed and control rats. Both BAL and histology data show that LPS-challenged lungs presented with dominating neutrophilic inflammation initially, which was resolved after 4 weeks. <bold>Conclusion:</bold> Longitudinal MRI and cell profiling after injury confirm that mixed leukocytes may be the trigger for progressive fibrosis, while pure neutrophilic inflammation successfully is resolved.