Research Reports - Variable neuroendocrine-immune dysfunction in individuals with unfavorable outcome after severe traumatic brain injury
Brain Behav Immun. 2014 Sep 16
Santarsieri M(1), Kumar RG(2), Kochanek PM(3), Berga S(4), Wagner AK(5)
Bidirectional communication between the immune and neuroendocrine systems is not
well understood in the context of traumatic brain injury (TBI). The purpose of
this study was to characterize relationships between cerebrospinal fluid (CSF)
cortisol and inflammation after TBI, and to determine how these relationships
differ by outcome. CSF samples were collected from 91 subjects with severe TBI
during days 0-6 post-injury, analyzed for cortisol and inflammatory markers, and
compared to healthy controls (n=13 cortisol, n=11 inflammatory markers).
Group-based trajectory analysis (TRAJ) delineated subpopulations with similar
longitudinal CSF cortisol profiles (high vs. low cortisol). Glasgow Outcome Scale
(GOS) scores at 6months served as the primary outcome measure reflecting global
outcome. Inflammatory markers that displayed significant bivariate associations
with both GOS and cortisol TRAJ (interleukin [IL]-6, IL-10, soluble Fas [sFas],
soluble intracellular adhesion molecule [sICAM]-1, and tumor necrosis factor
alpha [TNF]-α) were used to generate a cumulative inflammatory load score (ILS).
Subsequent analysis revealed that cortisol TRAJ group membership mediated ILS
effects on outcome (indirect effect estimate=-0.253, 95% CI (-0.481, -0.025),
p=0.03). Correlational analysis between mean cortisol levels and ILS were
examined separately within each cortisol TRAJ group and by outcome. Within the
low cortisol TRAJ group, subjects with unfavorable 6-month outcome displayed a
negative correlation between ILS and mean cortisol (r=-0.562, p=0.045).
Conversely, subjects with unfavorable outcome in the high cortisol TRAJ group
displayed a positive correlation between ILS and mean cortisol (r=0.391,
p=0.006). Our results suggest that unfavorable outcome after TBI may result from
dysfunctional neuroendocrine-immune communication wherein an adequate immune
response is not mounted or, alternatively, neuroinflammation is prolonged.
Importantly, the nature of neuroendocrine-immune dysfunction differs between
cortisol TRAJ groups. These results present a novel biomarker-based index from
which to discriminate outcome and emphasize the need for evaluating tailored
treatments targeting inflammation early after injury.