Traumatic brain injury (TBI) is characterized by high mortality and severe disability worldwide representing a major social, economic, and medical problem. Pathogenesis of secondary brain damage is underpinned by a cascade of neuroinflammatory reactions triggered by cytokine release. Key mediators include interleukin-6 (IL-6) and interleukin-2 (sIL-2R) system. However, their daily dynamics in acute period of severe trauma and relationship with intracranial hypertension remain poorly understood.
MATERIAL AND METHODS
The study was conducted at the Burdenko Neurosurgical Center. Inclusion criteria: acute TBI, admission within 24 hours, age 18—75 years. Exclusion criteria: atonic coma, decompensation of chronic diseases. IL-6, sIL-2R, C-reactive protein, and procalcitonin were assessed.
RESULTS
There were 74 patients with severe TBI (19 women, mean age 34.0±12.5 years). The mortality rate was 14.9% (11 patients). Biphasic cytokine dynamics was revealed. Early increase in IL-6 on day 1 reflected extent of primary injury. On the 2nd day, IL-6 levels remained significantly higher in patients with fatal outcome (median 40.2 vs. 22.4 pg/ml, p<0.05). Secondary increase was recorded after 3 days and coincided with manifestation of infectious complications peaking on day 5. On day 5, sIL-2R levels were found to be more than 2.5-fold higher in patients with fatal outcome (1660.0 vs. 649.0 pg/ml, p<0.05). In fatal patients, we found strong direct correlation between IL-6 and intracranial pressure (rho=0.71), as well as inverse correlation with cerebral perfusion pressure.
CONCLUSION
Biphasic cytokine response develops in acute phase of severe traumatic brain injury. Early phase (2 days) is characterized by increased IL-6 according to extent of primary cerebral injury. The second phase (days 3—14) is associated with infectious complications and characterized by increased sIL-2R and IL-6. It is not their absolute value, but temporal dynamics is prognostically significant. No IL-6 reduction by 48 hours after injury indicates uncontrollable neuroinflammation and potentially unfavorable outcomes. Peak (more than 2.5 times) increase in sIL-2R on day 5 is a marker of transformation of protective inflammation into systemic hyperinflammatory syndrome. Direct correlation between IL-6 and intracranial hypertension in fatal patients confirms pathogenetic role of this cytokine in secondary brain injury. IL-6 and sIL-2R monitoring may enable timely identification of patients with high risk of fatal intracranial hypertension and ensure a personalized approach to intensive care.
