Abstract
Background: Neuroinflammation following traumatic brain injury (TBI) has been shown to be associated with secondary injury development, however how systemic inflammatory mediators affect this is not fully understood. The aim of this study was to see how systemic inflammation affects markers of neuroinflammation, if this inflammatory response had a temporal correlation between compartments and how different compartments differ in cytokine composition.Methods: TBI patients recruited to a previous randomized controlled trial studying the effects of the drug anakinra (Kineret®), a human recombinant interleukin-1 receptor antagonist (rhIL1ra), were used (n=10 treatment arm, n=10 control arm). Cytokine concentrations were measured in arterial and venous samples twice a day, as well as in microdialysis-extracted brain extracellular fluid (ECF) following pooling every 6 hours. C-reactive protein level (CRP), white blood cell count (WBC), temperature and confirmed systemic clinical infection were used as systemic markers of inflammation. Principal component analyses, linear mixed-effect models, cross-correlations and multiple factor analyses were used.Results: The development of a systemic clinical infection results in an altered brain-ECF cytokine response (e.g. increase in G-CSF and decrease in PDGF-ABBB, p<0.05 respectively), even if adjusting for injury severity and demographic factors. rhIL1ra administration had a strong effect on the inflammatory response, independently altering different blood (n=6) and brain cytokine (n=3) levels. No substantial delayed temporal association between blood and brain compartments could be detected. Jugular and arterial blood held similar cytokine information content, but brain-ECF was markedly different. No clear arterial to jugular gradient could be seen.Conclusions: Systemic inflammation, and infection in particular, alters cerebral cytokine levels, and rhIL1ra administration potently affects both systemic and cerebral cytokine levels. Cerebral inflammatory monitoring provides independent information from arterial and jugular samples, which both demonstrate similar information content. These findings could present potential new treatment options in severe TBI patients, and stresses the need of adequate monitoring of inflammatory markers.
Systemic Inflammation Alters the Neuroinflammatory Response: A Prospective Clinical Trial in Traumatic Brain Injury.
