Relation of signal in mononuclear cell with endotoxin response and clinical outcome after trauma

Abstract

Background: We investigated the correlation of proinflammatory transcript nuclear factor κB (NF-κB) and antioxidative gene transcript nuclear factor-erythroid 2-related factor 2 (Nrf2) expressions in peripheral blood mononuclear cells (PBMCs) with the tumor necrosis factor α (TNF-α) response after endotoxin stimulation and the clinical outcome of severely injured patients.

Methods: Thirty-two severe blunt trauma patients (injury severity score>16) with systemic inflammatory response syndrome were enrolled. Age- and sex-matched healthy persons were the controls. Patients' blood samples were obtained at 24 and 72 hours after injury. Peripheral blood mononuclear cells were isolated, and measurements for NF-κB p65 translocation, Nrf2 and phosphorylated inhibitory κB-α expressions, and TNF-α levels were assayed after endotoxin stimulation.

Results: In the trauma patients, TNF-α hyporesponse, depressed NF-κB p65 translocation, and phosphorylated inhibitory κB-α expression in PBMCs were found at 24 and 72 hours after injury; the Nrf2 expressions in PBMCs were not significantly different between patients and controls. The TNF-α levels had significant correlation with the NF-κB translocation and the trend of negative correlation with Nrf2 expression. Fifteen patients had critical injury (injury severity score≥25). Patients with critical injury had a lower NF-κB signal and a lower TNF-α response than did the counter group. Twelve patients developed organ failure; their Nrf2 expressions were significantly lower than those of patients without organ failure.

Conclusions: The endotoxin hyporesponse associated with NF-κB and Nrf2 signal alternations in PBMCs of injured patients develops early after injury. The hyporesponse of PBMCs with a lower TNF-α level correlates with a lower NF-κB signal and is associated with critical injury, whereas a depressed Nrf2 expression in PBMCs is associated with later organ failure in trauma patients.