gms | German Medical Science

Objectives: The lung is commonly affected in polytraumatized patients. Direct organ damage, systemic and local inflammatory responses as well as choice of surgical stabilization influence the patients’ further clinical course. Modulation of the post-traumatic immune response by targeting the key innate immunity check point molecules complement C5 and TLR co-receptor CD14 may exert beneficial effects. Therefore, the present study investigated the effect C5/CD14 inhibition on alveolar macrophages (AMs) in relation to common surgical strategies for long bone fractures in polytraumatized patients.

Methods: In total, 26 pigs sustained blunt chest trauma, liver laceration, bilateral femur fractures, and haemorrhagic shock. Animals were operatively stabilized, using external fixation (EF, n=8) or intramedullary nailing (IN, n=8) and monitored under ICU-standards for 72 h. A third group (n=4) was treated with IN in combination with C5/CD14 inhibition. The control group consisted of six animals who received identical instrumentation, anaesthesia, mechanical ventilation, parental nutrition, and fluid administration. AMs were harvested via bronchoalveolar lavage at 72 h, isolated, and cultured for 24 h in complete medium containing 100 ng/mL LPS. Supernatant was analysed with multiplex assay of interferon (IFN)-alpha and -gamma, tissue necrosis factor (TNF), and interleukins (IL)-1beta, 4, 6, 8, and 10.

Results and conclusion: Compared to controls, the IN and EF groups showed a significant increase in pro-inflammatory cytokine levels (IL-1beta, IL-6, TNF). Notably, the IN+C5/CD14 inhibition group exhibited significantly lower concentrations of pro-inflammatory cytokines compared to the IN group, with concentrations comparable to the controls. Furthermore, although not significant, pro-inflammatory cytokine levels in the IN+C5/CD14 group were lower than in the EF group. For the anti-inflammatory cytokines IL-4 and IL10, a similar pattern was found in all groups. No significant differences in IFN-alpha, INF-gamma, and IL-8 concentrations were identified between the groups.

This study revealed treatment specific, pulmonary cytokine expression patterns in polytraumatized organisms with concomitant lung injury. These patterns were associated with surgical procedures and correlated to the novel C5/CD14 inhibition therapy. This study showed for the first time that IN+C5/CD14 inhibition is associated with a significant reduction of pro-inflammatory cytokine levels, potentially opening the door for a timely definitive fracture stabilization in this challenging population.