Impairment of the Complement Function After Multiple Trauma in Humans

Abstract

After multiple trauma, development of systemic inflammatory response and innate immune dysfunction have been described, reflected by disturbances of the cellular defense and uncontrolled activation of the complement system. However, little is known about the complement function during the early posttraumatic period (< 90 min after accident). Therefore, we investigated the complement status and function in sera from trauma victims (n=40 with an injury severity score of ISS=35.2 „b 3.1), obtained at the scene, immediately after admission in the emergency room (ER), 4h, 12h, 24h and 120h and 240h after trauma. There was a robust complement activation at the scene with significantly enhanced levels of the complement activation products C3a, C5a and MAC. While the serum levels of C3a were consistently elevated over the 10 day observation period, C5a and MAC concentrations dropped over time after the initial peak. There was also a significant loss of chemotactic activity up to 4h after injury. Complement function was assessed by the hemolytic activity of serum (CH50). At the scene, CH50 activity was impaired and virtually abolished in the ER, indicating consumption of complement within the first hours after trauma. Furthermore, a positive correlation between the loss of hemolytic activity at the scene and the 10 day outcome was found. In conclusion, the complement‐associated defence seems to be compromised rapidly after severe trauma, which may lead to the enhanced susceptibility and impairment of the innate immune response after trauma. This work was supported by NIH Grants No. GM‐61656, GM‐29507 and HL‐31963.

Polytrauma—pathophysiology and management principles

“…Furthermore, the degree of complement activation and development of a "complementopathy" (Fig. 2) seems to be crucial for the subsequent inflammatory response and the outcome of polytraumatized patients [8]. This is in accord with other reports, which suggested the use of the C3a/C3 ratio for scoring severity and outcome of trauma [9].…”

“…Our own studies have revealed that multiple injury is associated with extensive, uncontrolled activation of complement [8].…”

Conversion from external fixator to intramedullary nail causes a second hit and impairs fracture healing in a severe trauma model

“…It was previously shown that the complement system was rapidly activated after injury in the rat model of blunt chest trauma and triggered several downstream effects of the systemic inflammation, such as cytokine release and increased neutrophil numbers, phagocytosis, chemotaxis and respiratory burst induction 7. Clinically, the complement system is also rapidly activated after initial trauma,1, 26 with complement anaphylatoxins shown to be correlated with injury severity and mortality 1, 5, 27, 28. We showed that C5a serum levels increased during the first 24 h after the initial trauma and returned to baseline values after 72 h, independently of an additional blunt chest trauma.…”

C5aR‐antagonist significantly reduces the deleterious effect of a blunt chest trauma on fracture healing

“…In all cases the activation pathways lead to the production of the important anaphylatoxin C5a 9, 10. In trauma victims, systemic C5a immediately increased within minutes and was strongly correlated with injury severity 11, 12. C5a induces for example the migration of phagocytes, degranulation of mast cells, systemic cytokine release, respiratory burst induction, and the regulation of apoptosis in inflammatory cells, thus acting at the very first line of defense in the posttraumatic systemic inflammatory response 1.…”