Attenuating pulmonary injury and inflammation with C5/CD14 inhibition therapy: results from a porcine polytrauma model with blunt chest trauma

Thoracic injury is prevalent among polytrauma patients, affecting up to 45% of these patients and often leading to complications such as pulmonary dysfunction up to acute respiratory distress syndrome (ARDS). This study investigates the impact of surgical invasiveness and C5/CD14 inhibition therapy on pulmonary tissue damage and the local immune response of the lungs in a porcine polytrauma model. A post hoc analysis focusing on the pulmonary consequences of blunt thoracic trauma and multiple trauma was performed in a previously published porcine trauma model, in presence or absence of immunomodulation. A control group (n = 6; CG) was used that received identical instrumentation, anesthesia, nutrition, and fluid intake, but no trauma. For the trauma model, male pigs underwent a standardized polytrauma, followed by allocation into three treatment groups: early total care (n = 8; ETC), damage control orthopedics (n = 8; DCO), and ETC with C5/CD14 inhibition (n = 4). Pulmonary histopathological changes were assessed at 72 h after trauma through lung injury scores and wet/dry ratios, while ex vivo cytokine expressions from isolated alveolar macrophages (AMs) were analyzed using enzyme-linked immunosorbent assays. Histological results revealed significant lung damage in both the ETC and DCO groups compared to the control as well as the C5/CD14 inhibition group. The addition of C5/CD14 inhibition significantly lessened lung tissue damage, as indicated by lower lung injury scores and wet/dry ratios. Cytokine assays showed that AMs from the ETC + C5/CD14 group exhibited significantly decreased levels of proinflammatory cytokines compared to the other trauma groups, while showing similar cytokine expression levels as compared to the control group. Early double blockade of C5/CD14 effectively mitigates pulmonary tissue damage and post-traumatic inflammatory responses in lung tissue. This might result in reduced complications like ARDS and facilitating earlier definitive surgical interventions. These findings underscore the potential importance of immunomodulation strategies in managing post-traumatic outcomes and highlight the need for further research into their clinical applications in polytrauma settings.