Soluble receptors of tumor necrosis factor-α: early predictors of mortality in patients with severe burn injury

Introduction

Burn injury is associated with intense immunoinflammatory activity and release of mediators that perpetuate an inflammatory cascade causing damage to many organs. It appears that tumor necrosis factor (TNF)-α levels are related to poor prognosis in this condition. Endothelin (ET)-1 levels are also elevated but its role as a prognostic marker is unclear. However, early sequential profiling of circulating levels of TNF-α, TNF soluble receptors and of ET-1 in patients with burn injury remains poorly investigated. Early biologic markers of severity in these patients could be useful to support earlier and more aggressive therapeutic approaches.

Methods

Twenty patients with burn injury with total body surface area burned (TBSA) of 30% were enrolled within less than 6 h from the accident. Clinical variables were recorded. Blood samples were drawn at time zero, 6, 12, 24 h to sequentially measure TNF-α, TNF-α 1 and 2 soluble receptors (sTNFR1 and sTNFR2), and ET-1 levels using ELISA assays. All patients were followed up to hospital discharge.

Results

Age, TSBA and inhalation injury were not significantly different among survivors (n = 10; 30 ± 13 years, TSBA 40 ± 12%) and nonsurvivors (n = 11, 38 ± 15 years, TSBA 56 ± 20%). As expected, APACHEII and multiple organ dysfunction syndrome scores were significantly higher in nonsurvivors (15.4 ± 6.2 and 2.6 ± 1.6) compared to survivors (9.8 ± 5.2 and 0.44 ± 0.7) (P = 0.048 and P = 0.002, respectively). Levels of TNF-α and ET-1 were similarly elevated in both groups in all time-points. sTNFR1 levels, however, were increased in nonsurvivors (2937 ± 1676 pg/ml; 4548 ± 1436 pg/ml) compared to survivors (1313 ± 561 pg/ml; 2561 ± 804 pg/ml) at 6 h and 24 h, respectively (P = 0.01 and P = 0.002). sTNFR2 levels were significantly increased in nonsurvivors (4617 ± 1876 pg/ml) versus survivors (2611 ± 1326 pg/ml) only at 6 h (P = 0.015). Elevated levels of sTNFR1 at 6 h and of TNF-α at 12 h configured positive (100% for both markers) and negative predictive values for mortality of 70 and 52%, respectively (relative risk 3.25 and 1.2, respectively; confidence intervals 1.4-7.3 and 1.28-3.52, respectively). Significant correlations between APACHEII scores and biological markers, especially sTNFR1 and ET-1, at early time points were observed. TSBA correlated only with sTNFR1 and TNF-α at 12 h.

Conclusion

TNF-α and ET-1 levels did not appear to be increased in nonsurvivors compared to survivors. Alternatively, increased levels of sTNFR1 and sTNFR2 were consistently higher at 6 h in nonsurvivor patients with burns. Clinical parameters of severity were associated to high biological markers levels. Very early determination of sTNFR1 and sTNFR2 may help to identify patients at higher risk for adverse outcome in severe burn injury.