Brain Death-Induced Inflammatory Activity is Similar to Sepsis-Induced Cytokine Release

Abstract

Brain death (BD) is associated with a systemic inflammation leading to worse graft outcomes. This study aimed to compare plasma cytokine values between brain-dead and critically ill patients, including septic and non-septic controls, and evaluate cytokine release kinetics in BD. Sixteen brain-dead and 32 control patients (16 with and 16 without sepsis) were included. Plasma cytokines were measured by magnetic bead assay after the first clinical exam consistent with BD and every 6 hours thereafter, and at the time of study entry in the control group. The values for IL-8 and IFN-γ were higher in brain-dead and septic patients than in non-septic patients [IL-8: 80.3 (18.7-169.6) vs. 68.2 (22.4-359.4) vs. 16.4 (9.2-42.7) pg/mL; P = 0.006; IFN-γ: 2.8 (1.6-6.1) vs. 3.4 (1.2-9.0) vs. 0.5 (0.5-1.8) pg/mL; P = 0.012]. TNF showed a clear tendency to increase in brain-dead patients [2.7 (1.0-4.8) vs. 1.0 (1.0-5.6) vs. 1.0 (1.0-1.0) pg/mL; P = 0.051], and IL-6 values were higher in brain-dead patients than in non-septic controls [174.5 (104.9-692.5) vs. 13.2 (7.3-38.6) pg/mL; P = 0.002]. These differences remained even after excluding brain-dead patients who also had sepsis ( n = 3). IL-1β and IL-10 values increased from baseline to time point 2 (∼6 hours later) [IL-1β: 5.39 (1.93-16.89) vs. 7.11 (1.93-29.13) pg/mL; P = 0.012; IL-10: 8.78 (3.62-16.49) vs. 15.73 (5.49-23.98) pg/mL; P = 0.009]. BD-induced and sepsis-induced plasma cytokine values were similarly high, and both were higher than the observed in non-septic critically ill patients.

Keywords: brain death; critical illness; inflammation; cytokines; sepsis.

Fig 1.

Plasma cytokine values determined by magnetic bead assay in brain-dead patients and controls. A. Tumor necrosis factor (pg/mL). B. Interleukin-1β (pg/mL). C. Interleukin-6 (pg/mL). D. Interleukin-8 (pg/mL). E. Interleukin-10 (pg/mL). F. Interferon-γ (pg/mL). Kruskal–Wallis with pairwise comparison. Statistically significant differences as indicated by the bars (IL-6: P = 0.01 for BD vs. non-septic controls; IL-8: P = 0.029 for BD vs. non-septic controls and P = 0.01 for septic vs. non-septic controls; IFN-γ: P = 0.028 for BD vs. non-septic controls and P = 0.031 for septic vs. non-septic controls). Graphs are plotted on a logarithmic scale, representing median and interquartile range. Dots and asterisks represent outliers.