Relevance of cerebral interleukin-6 after aneurysmal subarachnoid hemorrhage.
BACKGROUND
This study examines the inflammatory response via interleukin-6 (IL-6) in aneurysmal subarachnoid hemorrhage (aSAH) patients and its association with their clinical course (occurrence of acute focal neurological deficits, AFND; and delayed cerebral ischemia, DCI).


METHODS
A total of 38 consecutive aSAH patients were studied prospectively within 14 days after admission and classified as asymptomatic (n = 9; WFNS grade 1 (1-2), median and quartiles) and symptomatic (n = 29; WFNS grade 4 (2-5)); the latter presenting with AFND (n = 13), DCI (n = 10) or both (n = 6). Levels of pro-inflammatory cytokine IL-6 were determined in cerebral extracellular fluid (ECF, using cerebral microdialysis), cerebrospinal fluid (CSF) and plasma for 10 days after aSAH. Additionally, C-reactive protein (CRP) levels were measured in plasma.


RESULTS
High IL-6 levels in CSF, ECF and plasma were found in all patients, reflecting a pronounced local inflammatory response after aSAH, followed only in symptomatic patients by a delayed systemic inflammation (CRP P < 0.025, days 7-9 after aSAH). In all compartments, IL-6 levels appeared to be higher in symptomatic patients, accompanied also by a higher ECF lactate-pyruvate ratio (P = 0.04). Cerebral, but not plasma IL-6, levels were indicative of the development of DCI in symptomatic patients (ECF P = 0.003; CSF P = 0.001).


CONCLUSIONS
A pronounced initial cerebral inflammatory state was observed in patients of all WFNS grades, suggesting that IL-6 elevations are not necessarily detrimental. Cerebral, but not plasma IL-6, levels were predictive of the development of delayed ischemic deficits in symptomatic patients, suggesting that CSF or ECF are the best sampling media for future studies.
Sarrafzadeh
Asita
A
Department of Neurosurgery, Campus Virchow Medical Center, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. asita.sarrafzadeh@charite.de
Schlenk
Florian
F
Gericke
Christine
C
Vajkoczy
Peter
P
D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D002545:Brain Ischemia / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology; D002097:C-Reactive Protein / Q000378:metabolism; D003422:Critical Care / Q000379:methods; D004660:Encephalitis / Q000134:cerebrospinal fluid* / Q000276:immunology*; D045604:Extracellular Fluid / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000134:cerebrospinal fluid*; D019344:Lactic Acid / Q000134:cerebrospinal fluid; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D019289:Pyruvic Acid / Q000134:cerebrospinal fluid; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000134:cerebrospinal fluid* / Q000276:immunology*
D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D019344:Lactic Acid; D019289:Pyruvic Acid; D002097:C-Reactive Protein