Immune modulation mimics damage control orthopaedics' upregulation of anti-inflammatory miRNA-21/23a/27a and miRNA-30b in the lung after polytrauma in pigs.

purposeBlunt chest trauma is common in polytraumatised patients and often leads to respiratory distress. Moreover, the systemic inflammation resulting from the trauma itself, along with subsequent surgical interventions, further contributes to pulmonary dysfunction. Therefore, modulating post-traumatic immune responses may offer potential benefits. MicroRNAs may influence the activation and progression of regenerative responses following polytrauma and could serve as potential modulators. This study investigates the expression of a selection of miRNAs with known involvement in pulmonary pathologies relevant for the post-trauma setting, in a porcine polytrauma model comparing two surgical treatment groups and one treatment group that additionally received a drug-based treatment based on combined inhibition of complement component C5 and the Toll-like co-receptor CD14.

methodsThe porcine polytrauma model consisted of blunt chest trauma, bilateral femur fractures, liver laceration, and haemorrhagic shock. Four groups were defined: sham, early total care (ETC: n = 8), damage control orthopaedics (DCO: n = 8), ETC with C5/CD14 inhibition (n = 4). Animals were monitored and guideline-treated in an ICU setting for 72 h. After sacrifice, lung samples were taken from the left lobe. MiRNAs were analysed by qPCR. Furthermore, Periodic Acid Schiff staining and in situ hybridisation were performed.

resultsMiRNAs associated with lung function, inflammation, and fibrosis were analysed. Compared to ETC, DCO 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 C5/CD14 inhibitors to ETC further reduced the expression of inflammatory and fibrotic microRNAs compared to both DCO and ETC and revealed a significant reduction in histopathological changes in the lung tissue.

conclusionThis study indicates that combined inhibition of C5 and CD14 effectively reduces posttraumatic histopathological changes in lung tissue associated with less inflammatory and fibrotic miRNA expression, compared to both the DCO and ETC groups.