Background Increased intracranial pressure (ICP) is a serious life-threatening secondary event following traumatic brain injury (TBI). 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. Results Consistent 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 CSNK1E 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 Pafuramidine 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. Conclusions Our results suggest that serum IL-6 can be used for the differential diagnosis of elevated ICP in isolated TBI. Background Traumatic brain injury (TBI) is a leading cause of morbidity and mortality among civilian and military populations. The initial injury sets in motion a number of cellular and molecular events leading to the development of secondary processes that profoundly influence outcome. One of the major secondary pathologies is elevated intracranial pressure (ICP). If not maintained below 20 mm Hg elevated ICP can cause poor cerebral perfusion brain herniation and death. In many cases ICP rises in a delayed manner reaching its peak level between days 3-5 post-TBI . Although no prophylactic treatment is currently available to prevent elevated ICP neurointensivists and neurosurgeons often use sedatives mannitol hypertonic saline cerebrospinal fluid drainage decompressive craniectomy and/or barbiturate-induced coma to manage this condition. Therefore the identification of prognostic biomarkers that can predict which patients Pafuramidine are at risk of developing high ICP would Pafuramidine help in managing severe TBI patients. Previous studies have implicated inflammatory processes in ICP elevation [2 3 Both pro- and anti-inflammatory cytokines have been reported to change as a result of TBI and their combined action is thought to determine the overall degree of inflammation . Interleukin-6 (IL-6) is a 20-30 kDa cytokine with pleiotropic properties that has been shown to be a biomarker associated with various disease states. For example high serum IL-6 correlates with coronary instability and carotid plaques has been shown to be a prognostic marker for septic shock and is an indicator of outcome in severe intra-abdominal sepsis [5-7]. In TBI a relationship has been reported between the transcranial IL-6 gradient (venous-arterial) at the time of admission and survivability . In addition a recent multiplex analysis of putative serum biomarkers identified IL-6 as a marker of inflicted pediatric TBI . Although these studies support the premise that inflammation-related proteins such as IL-6 are elevated following TBI it has not been examined if the magnitude or duration of induction correlates with the development of ICP. In the present study we utilized two screening methods antibody arrays and multiplexing to evaluate the levels of interleukin family members in the serum of healthy volunteers and in severe TBI patients (GCS≤8) with and without incidence of ICP. Consistent with a number of previous reports we observed elevated IL-6 levels in TBI patients as compared to healthy volunteers. Interestingly the group of TBI patients who subsequently developed ICP ≥ 25 mm Hg had significantly higher serum IL-6 levels within the first 17 hours of injury as compared to Pafuramidine the patients whose ICP remained ≤20 mm Hg during their hospital stay. Pafuramidine However in polytrauma patients with TBI serum IL-6 levels were unable to differentiate between the two groups..