Interleukin-6 as a prognostic biomarker of clinical outcomes after traumatic brain injury: a systematic review

Abstract

Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. There are currently no early biomarkers for prognosis in routine clinical use. Interleukin-6 (IL-6) is a potential biomarker in the context of the established role of neuroinflammation in TBI recovery. Therefore, a systematic review of the literature was performed to assess and summarise the evidence for IL-6 secretion representing a useful biomarker for clinical outcomes. A multi-database literature search between January 1946 and July 2021 was performed. Studies were included if they reported adult TBI patients with IL-6 concentration in serum, cerebrospinal fluid (CSF) and/or brain parenchyma analysed with respect to functional outcome and/or mortality. A synthesis without meta-analysis is reported. Fifteen studies were included, reporting 699 patients. Most patients were male (71.7%), and the pooled mean age was 40.8 years; 78.1% sustained severe TBI. Eleven studies reported IL-6 levels in serum, six in CSF and one in the parenchyma. Five studies on serum demonstrated higher IL-6 concentrations were associated with poorer outcomes, and five showed no signification association. In CSF studies, one found higher IL-6 levels were associated with poorer outcomes, one found them to predict better outcomes and three found no association. Greater parenchymal IL-6 was associated with better outcomes. Despite some inconsistency in findings, it appears that exaggerated IL-6 secretion predicts poor outcomes after TBI. Future efforts require standardisation of IL-6 measurement practices as well as assessment of the importance of IL-6 concentration dynamics with respect to clinical outcomes, ideally within large prospective studies. Prospero registration number: CRD42021271200

Neuroinflammatory Biomarkers for Traumatic Brain Injury Diagnosis and Prognosis: A TRACK-TBI Pilot Study

“… 53 TBI-induced microglial activation and increased expression of proinflammatory mediators, such as HMGB-1 and IL-6, have been associated with cerebral edema and neurological deficits. 16 , 54 Our results support the likelihood of HMGB-1 as a marker for brain-specific trauma in humans. The correlations identified in our study underscore the complex crosstalk among markers of neuroinflammation and secondary injury and inform the development of biomarker “panels” for validation in acute and chronic TBI.…”

Reactive gliosis in traumatic brain injury: a comprehensive review

“…Nevertheless, compounds produced by activated astrocytes may play both detrimental and protective roles. For example, IL-6 is a proinflammatory cytokine, that is overexpressed during TBI and has a key role in mediating neuroinflammation ( Yang et al, 2013 ; Edwards et al, 2020 ; Ooi et al, 2022 ). In contrast, astrocytic overexpression of IL-6 is beneficial for wound closure and causes a decrease in oxidative stress and apoptosis in the TBI cryo-lesion model ( Penkowa et al, 2003 ).…”

Intergenerational Perioperative Neurocognitive Disorder

“…Traumatic brain injury, with >50 million cases per year, is a dominant cause of disability in young adults [ 371 , 372 , 373 ], many of whom will have children later. The pathophysiology of TBI involves excessive dysregulation of stress response systems, neuroinflammation, and cognitive decline [ 366 , 368 , 369 , 372 , 373 , 374 , 375 , 376 , 377 , 378 , 379 , 380 , 381 ]. Patients with a history of TBI frequently require general anesthesia/surgery or sedation to treat conditions unrelated to TBI or injuries that may occur at the time of TBI.…”