Serum IL-6: a candidate biomarker for intracranial pressure elevation following isolated traumatic brain injury

Abstract

BackgroundIncreased intracranial pressure (ICP) is a serious, life-threatening, secondary event following traumatic brain injury (TBI). In many cases, ICP rises in a delayed fashion, reaching a maximal level 48-96 hours after the initial insult. While pressure catheters can be implanted to monitor ICP, there is no clinically proven method for determining a patient's risk for developing this pathology.MethodsIn the present study, we employed antibody array and Luminex-based screening methods to interrogate the levels of inflammatory cytokines in the serum of healthy volunteers and in severe TBI patients (GCS≤8) with or without incidence of elevated intracranial pressure (ICP). De-identified samples and ELISAs were used to confirm the sensitivity and specificity of IL-6 as a prognostic marker of elevated ICP in both isolated TBI patients, and polytrauma patients with TBI.ResultsConsistent with previous reports, we observed sustained increases in IL-6 levels in TBI patients irrespective of their ICP status. However, the group of patients who subsequently experienced ICP ≥ 25 mm Hg had significantly higher IL-6 levels within the first 17 hours of injury as compared to the patients whose ICP remained ≤20 mm Hg. When blinded samples (n = 22) were assessed, a serum IL-6 cut-off of <5 pg/ml correctly identified 100% of all the healthy volunteers, a cut-off of >128 pg/ml correctly identified 85% of isolated TBI patients who subsequently developed elevated ICP, and values between these cut-off values correctly identified 75% of all patients whose ICP remained ≤20 mm Hg throughout the study period. In contrast, the marker had no prognostic value in predicting elevated ICP in polytrauma patients with TBI. When the levels of serum IL-6 were assessed in patients with orthopedic injury (n = 7) in the absence of TBI, a significant increase was found in these patients compared to healthy volunteers, albeit lower than that observed in TBI patients.ConclusionsOur results suggest that serum IL-6 can be used for the differential diagnosis of elevated ICP in isolated TBI.

Prognostic factors of neuroinflammation and oxidative stress in brain injury patients at Cipto Mangunkusumo Hospital Jakarta

“…Neurosurgical procedures aim to reduce intracranial pressure. In accordance with the study of Hergenroeder et al, 16 high intracranial pressure is correlated with increased levels of IL-6. Intracranial pressure release after neurosurgical procedure can be ascribed to improvement of neuroinflammatory processes.…”

“…Intracranial pressure release after neurosurgical procedure can be ascribed to improvement of neuroinflammatory processes. 16 After 3 months of follow up, lower post-operative IL-6 levels (under 100 pg/mL) have 11.6-times higher chance of reaching the 3 months post-trauma GOS 'favorable'.…”

High Mobility Group Box 1 and Traumatic Brain Injury

“…Thus, the coordination of both MMP-2/9 and iNOS may elucidate the protective effects of antiHMGB1mAb. Hergenroeder et al also indicated that increase levels of CSF and serum concentrations of IL-6, a microglial-derived cytokine, significantly associated with neuronal injury and increased ICP after TBI in human [41].…”

Temporal Profile of Cerebrospinal Fluid, Plasma, and Brain Interleukin-6 After Normothermic Fluid-Percussion Brain Injury: Effect of Secondary Hypoxia

“…For example, in a recent study where animals were subjected to closed head injury, femoral fracture, and hemorrhagic shock, an increased inflammation, including elevated blood levels of IL-6 were reported compared to animals undergoing TBI alone (Probst et al, 2012). In clinical studies where secondary insults may be common, IL-6 has been reported to be an effective biomarker for brain injury severity and may be predictive for a delayed increase in intracranial pressure (Kim et al, 2000;Woiciechowsky et al, 2002;Hergenroeder et al, 2010).…”