Trauma treatment and C5/CD14 inhibition influence pulmonary miRNA expression and histopathological changes in the lung after blunt chest trauma

Introduction Blunt chest trauma is common in polytraumatized patients. Systemic inflammation due to the trauma and subsequent surgical interventions further contribute to pulmonary dysfunction. Modulation of the post-traumatic innate immune response may offer therapeutic benefits in the treatment of polytrauma patients. The aim of this study was to investigate the effect of C5/CD14 inhibition on pulmonary microRNA (miRNA) expression, and subsequent histological changes in the lung parenchyma. Materials & methods The polytrauma model (pig) included blunt chest trauma, bilateral femur fractures, liver laceration, and haemorrhagic shock. Four groups were defined: sham (n=6), external fixation (EF, n=8), intramedullary nailing (IMN, n=8), and IMN with C5/CD14 inhibition (IMN+anti-C5/CD14, n=4). Animals were monitored and treated in an ICU-setting including volume-controlled, mechanical ventilation for 72 hours. After sacrifice, lung samples were taken from the left lobe. MiRNAs were isolated, transcribed, and analysed by qPCR. Furthermore, Periodic Acid Schiff (PAS) staining and in situ hybridization was performed. Results MiRNAs associated with lung function, inflammation, and fibrosis were analysed. Compared to IMN, EF resulted in less inflammatory and fibrotic miRNA expression, consistent with histological findings showing more preserved alveoli, less septal thickening, and fewer inflammatory cell infiltrations. The addition of anti-C5/CD14 to IMN further reduced the expression of inflammatory and fibrotic microRNAs compared to both EF and IMN and showed a significant reduction in histopathological changes in the lung tissue.Conclusion This study showed that anti-C5/CD14 therapy effectively reduced histopathological changes in the lung tissue combined with less inflammatory and fibrotic miRNA expression, compared to both the EF and IMN groups. Further research should focus on the long-term effects of this dual therapy on tissue regeneration in the polytrauma patient.

This research was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 429837092.