Abstract
Objective. To investigate the influence of traumatic brain injury (TBI) on immune function and viability of human peripheral monocytes in polytraumatized patients. Material and methods. This was a prospective, randomized, controlled clinical study conducted in a Level I trauma center. Multiply injured patients (n=42; mean age 42.4±15.5 years) with a mean Injury Severity Score (ISS) of 32.3±9.6 were compared to healthy controls (n=20; mean age 36.3±8.4 years). The methods used were clinical evaluation, scoring of injury severity (ISS, abbreviated injury scores), multiple organ dysfunction score, real-time reverse transcription polymerase chain reaction, Western blotting and fluorescent-activated cell sorting analyses of negatively isolated monocytes. The main outcome measures were overall clinical outcome, terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) staining, expression of the Fas and tumor necrosis factor receptor I, expression of the mitochondrial proteins Bax and Bcl-2, caspase-8, -9 and -3/7 activity and the level of C5a throughout a 5-day post-trauma observation period. Results. Apoptosis of peripheral blood monocytes was evident in both patient cohorts, as demonstrated by positive TUNEL staining and significant increases in caspase-3/7 activation. Trauma patients with TBI (+TBI patients) presented with a higher incidence of sepsis. Moreover, only +TBI patients demonstrated significant upregulation of pro-apoptotic mediators (increased Fas receptor) and downregulation of anti-apoptotic mediators (decreased Bcl-2) via caspase-dependent signaling (increased caspase-8 and -9) when compared to both trauma patients without TBI (−TBI patients) and healthy controls. In contrast, −TBI patients demonstrated significantly higher plasma concentrations of anaphylatoxin C5a on Day 0. Conclusions. Multiply injured patients show significant monocyte apoptosis, which may particularly promote the development of post-traumatic complications in a caspase-dependent manner in +TBI patients. The role of increased C5a and complement-associated monocyte apoptosis in −TBI patients requires further investigation.