Early IL-6 plasma concentrations correlate with severity of brain injury and pneumonia in brain-injured patients.
BACKGROUND
Brain injury as well as early inflammatory and endocrine responses were found to be indicators for infectious complications in patients with multiple injuries. In this context, brain-derived inflammatory response as well as centrally triggered neuroendocrine activation and systemic immunodepression seem to be of major importance. Therefore, we hypothesize that a circulating index of inflammatory or endocrine function measured soon after brain injury (in patients with admission Glasgow Coma Scale [GCS] score of 4-7) would discriminate severe from moderate injury as indexed by GCS status on postinjury day 7.


METHODS
In a retrospective study, 25 patients with either acute traumatic brain injury or cerebral hemorrhage and an initial GCS score of 4 to 7 were examined. Blood samples were obtained at different time points, and different immune variables and neuroendocrine hormones were determined. According to the GCS score on day 7, patients were divided into two groups (GCS score > or = 8, moderate brain injury; and GCS score < 8, severe brain injury or patients who died within the first week) for comparison of variables. Concluding from the results of this retrospective analysis, in a prospective study patients (n = 26) were divided into two groups according to their interleukin (IL)-6 plasma concentrations on day 1 (IL-6 > or = 100 pg/mL and IL 6 < 100 pg/mL). After 7 days, the GCS score, the infection rate, and the mortality were compared between these two groups.


RESULTS
In the retrospective study, we could show that severe brain injury (as assessed by GCS score and mortality on day 7) was associated with high plasma levels of pro- and anti-inflammatory cytokines, acute phase proteins, and neuroendocrine hormones within 2 to 6 hours after the acute event. Among the investigated variables, elevated IL-6 plasma concentrations were stable up to 1 day after the acute event with a high predictive value with regard to the short-term prognosis and incidence of infectious complications within the first week. Because of this stability during the first 24 hours, we selected IL-6 for further studies. In the prospective study with a calculated cut-off IL-6 plasma concentration of 100 pg/mL on day 1, the predictive value of this parameter regarding the severity of the brain injury was fully confirmed (positive predictive value, 0.94; this value represents the observed pretest probability of 0.62). All patients who died (n = 5) or developed infectious complications within the first week (n = 8) showed plasma IL-6 levels > or = 100 pg/mL on day 1.


CONCLUSIONS
The IL-6 plasma level 1 day after the acute event with a cut-off of 100 pg/mL (Immulite) seems to be a predictor for short-term prognosis and infectious complications in brain-injured patients.
Woiciechowsky
Christian
C
Department of Neurosurgery, Charité-Campus Virchow-Klinikum, Humboldt University of Berlin, Berlin, Germany. christian.woiciechowsky@charite.de
Schöning
Britta
B
Cobanov
Jacqueline
J
Lanksch
Wolfgang R
WR
Volk
Hans-Dieter
HD
Döcke
Wolf-Dieter
WD
D000328:Adult; D000368:Aged; D015415:Biomarkers; D001930:Brain Injuries / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000401:mortality; D002543:Cerebral Hemorrhage / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000401:mortality; D016207:Cytokines / Q000097:blood; D005260:Female; D005858:Germany / Q000453:epidemiology; D006728:Hormones / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000453:epidemiology / Q000209:etiology*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D015599:Trauma Severity Indices
D015415:Biomarkers; D016207:Cytokines; D006728:Hormones; D015850:Interleukin-6