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


METHODS
In 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<or=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.


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 >or= 25 mm Hg had significantly higher IL-6 levels within the first 17 hours of injury as compared to the patients whose ICP remained <or=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 <or=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.


CONCLUSIONS
Our results suggest that serum IL-6 can be used for the differential diagnosis of elevated ICP in isolated TBI.
Hergenroeder
Georgene W
GW
The Department of Neurobiology and Anatomy, The University of Texas Medical School, Houston, Texas, USA. Georgene.W.Hergenroeder@uth.tmc.edu
Moore
Anthony N
AN
McCoy
J Philip
JP
Samsel
Leigh
L
Ward
Norman H
NH
Clifton
Guy L
GL
Dash
Pramod K
PK
D018806:APACHE; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001930:Brain Injuries / Q000097:blood* / Q000150:complications; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D050723:Fractures, Bone / Q000097:blood; D015600:Glasgow Coma Scale; D006801:Humans; D015601:Injury Severity Score; D015850:Interleukin-6 / Q000097:blood*; D019586:Intracranial Hypertension / Q000097:blood* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009104:Multiple Trauma / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D011933:Reagent Kits, Diagnostic; D011999:Recruitment, Neurophysiological / Q000502:physiology; D015203:Reproducibility of Results; D014057:Tomography, X-Ray Computed; D055815:Young Adult
D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; D011933:Reagent Kits, Diagnostic