Abstract
BackgroundSevere blunt chest trauma is associated with high mortality. Sepsis represents a serious risk factor for mortality in acute respiratory distress syndrome (ARDS). In septic patients with ARDS complement activation products were found to be elevated in the plasma. In single models like LPS or trauma complement has been studied to some degree, however in clinically highly relevant double hit models such as the one used here little data is available. Here, we hypothesized that absence of C5 is correlated with a decreased inflammatory response in trauma induced septic acute lung injury.Methods12 hrs after DH in mice the local and systemic cytokines and chemokines were quantified by multiplex bead array or ELISA, activated caspase-3 by western blot. Data were analyzed using one-way ANOVA followed by post-hoc Sidak’s multiple comparison test (significance, p≤ 0.05).ResultsIn lung tissue interleukin (IL)-6, monocyte chemo attractant protein-1 (MCP-1) and granulocyte-colony stimulating factor (G-CSF) was elevated in both C5-/- mice and wildtype littermates (wt), whereas caspase-3 was reduced in lungs after DH in C5-/- mice. Systemically, reduced keratinocyte-derived chemokine (KC) levels were observed after DH in C5-/- compared to wt mice. Locally, lung myeloperoxidase (MPO), protein, IL-6, MCP-1 and G-CSF in brochoalveolar lavage fluid (BALF) were elevated after DH in C5-/- compared to wt.ConclusionsIn the complex but clinically relevant DH model the local and systemic inflammatory immune response features both, C5-dependent and C5-independent characteristics. Activation of caspase-3 in lung tissue after DH was C5-dependent whereas local inflammation in lung tissue was C5-independent.
Highlights
Severe chest trauma is associated with approximately one quarter of all trauma-related deaths [1]
In lung tissue interleukin (IL)-6, monocyte chemo attractant protein-1 (MCP-1) and granulocyte-colony stimulating factor (G-CSF) was elevated in both C5-/- mice and wildtype littermates, whereas caspase-3 was reduced in lungs after Double hit (DH) in C5-/- mice
Reduced keratinocyte-derived chemokine (KC) levels were observed after DH in C5-/- compared to wt mice
Summary
Severe chest trauma is associated with approximately one quarter of all trauma-related deaths [1]. The development of acute lung injury (ALI) in critically ill trauma patients independently contributes to elevated in-hospital mortality [2]. Sepsis represents a serious risk factor for a mortality rate up to 50% in acute respiratory distress syndrome (ARDS) [3]. Wt and C5 (C5-/-) knock out mice had comparable survival rates [7] These observations suggest, that abrogated interaction of C5a with its receptors is somehow protective in polymicrobial sepsis but not the complete absence of C5 and its downstream complement products. Clinical studies revealed that complement activation occurs in lungs during ARDS development [10]. Sepsis represents a serious risk factor for mortality in acute respiratory distress syndrome (ARDS). In septic patients with ARDS complement activation products were found to be elevated in the plasma. We hypothesized that absence of C5 is correlated with a decreased inflammatory response in trauma induced septic acute lung injury.
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