Kinetics of the innate immune response after trauma: implications for the development of late onset sepsis

BACKGROUND: Severe trauma is characterized by a pronounced immunologic response with both proinflammatory and anti-inflammatory characteristics. The clinical course of trauma patients is often complicated by late-onset (>5 days) sepsis. However, the underlying mechanisms remain poorly defined. Here we studied the kinetics of systemic activation of neutrophils and monocytes following injury in trauma patients in the context of development of sepsis.

METHODS: Thirty-six severely injured patients were included and followed up for 10 days in the intensive care unit. Serial blood samples were taken daily and analyzed ex vivo for activation of PMNs (polymorphonuclear leukocytes, i.e., neutrophils) (expression MAC-1 [macrophage-1 antigen], CXCR-1 [CXC-chemokine receptor 1], FcγRII) and expression of human leukocyte antigen DR (HLA-DR) on monocytes. In addition, the functionality of PMNs was measured by activation of the respiratory burst and responsiveness for the innate immune stimulus N-formyl-methionyl-leucyl-phenylalanine (fMLF).

RESULTS: Ten of 36 patients developed septic shock, invariably 8 to 10 days after admission. CXCR-1 and fMLF-induced active FcγRII showed a gradual decrease in expression before clinical signs of septic shock. Patients who developed septic shock demonstrated a statistically significantly decreased fMLF-induced active FcγRII (P = 0.009) at initial presentation. An immediate decreased percentage of HLA-DR-positive monocytes could be contributed to an increased absolute number of HLA-DR-negative monocytes.

CONCLUSIONS: Phenotyping blood PMNs enables identification of the kinetics and magnitude of the initial systemic inflammatory response after injury. The decreased functionality of PMNs and monocytes reaches its minimum before the development of sepsis and could be an important contributing factor. This could support the early identification of patients at risk.