Proinflammatory versus anti-inflammatory cytokine profiles as an early predictor of outcome in severe multiple trauma

Introduction

In the present study we investigated the early prognostic value of the serum levels of the main proinflammatory and anti-inflammatory cytokines and soluble cytokine inhibitors for mortality and late complications such as sepsis and multiorgan failure (MOF) in a well-defined population of patients with severe trauma.

Methods

A total of 62 previously healthy immunocompetent patients with severe multiple trauma (ISS > 16) admitted to the Emergency Room and aged less than 65 years were included during a period of 18 months. Sixty-four healthy individuals served as controls. Sera for sequential cytokine determination from patients were obtained on admission, 12 hours and 24 hours after trauma. We used an ELISA kit for quantitative determination of a wide spectrum of proinflammatory and anti-inflammatory cytokines simultaneously (TNFα, IL-1β, IL-6, IL-10, sTNFR type I and type II, IL-1ra and TGFβ). All patients were evaluated clinically and microbiologically and were followed up for clinical outcome until discharge from the hospital.

Results

The patient characteristics (57 men and five women) were age 34.51 ± 11.65 years and ISS 22.16 ± 12.43. They had a mortality rate of 11.29%, MOF 22.58%, ARDS 8.06% and sepsis 33.87%. On admission, trauma patients had significantly higher levels of IL-6, IL-10, sTNFRII, IL-1ra and TGFβ than did controls. Among the various cytokines, IL-6 (admission, 12 hours, 24 hours) and IL-10 (24 hours) were more closely related to the severity of trauma and the ISS (P < 0.001). Elevated serum IL-6 (24 hours), TGFβ (admission) and IL-1ra (24 hours) were associated with intrahospital death, whereas higher levels of IL-6 (24 hours), IL-10 (24 hours), sTNFRI (24 hours), sTNFRII (12 hours and 24 hours) and IL-1ra (24 hours) were detected in patients who developed later sepsis and higher levels of IL-6 (admission, 12 hours and 24 hours), IL-10 (12 hours and 24 hours) and IL-1ra (12 and 24 hours) were detected in patients who developed later MOF. In the multivariate analysis, higher values of IL-6 (12 hours and 24 hours) were detected in sepsis and MOF (P = 0.006 and P = 0.029, respectively). In addition a significant decline in IL-10 at 12 hours and 24 hours was observed in patients without sepsis and MOF, as well as a decline in IL-1ra at 24 hours in survivors.

Conclusion

The levels of IL-6 as well as a sustained IL-10 and IL-1ra production may predict death and late complications as early as into the first 24 hours following severe trauma.