Relevance of Cerebral Interleukin-6 After Aneurysmal Subarachnoid Hemorrhage
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).
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.
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).
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.
KeywordsInflammation Interleukin-6 Cerebral metabolism Microdialysis Subarachnoid hemorrhage Infection
The authors acknowledge outstanding technical assistance by Sabine Seidlitz and Jasmin Kopetzki and the excellent support of the ICU team.
The authors have no financial interest in the monitoring device described.
- 14.Drake C. Report of World Federation of Neurological Surgeons Committee on a Universal Subarachnoid Hemorrhage Grading Scale. J Neurosurg. 1988;68:985–6.Google Scholar
- 22.Sarrafzadeh A, Haux D, Sakowitz O, Benndorf G, Herzog H, Kuechler I, et al. Acute focal neurological deficits in aneurysmal subarachnoid hemorrhage: relation of clinical course, CT findings, and metabolite abnormalities monitored with bedside microdialysis. Stroke. 2003;34:1382–8.CrossRefPubMedGoogle Scholar
- 25.Graetz D, Nagel A, Schlenk F, Sakowitz O, Vajkoczy P, Sarrafzadeh A. High ICP as trigger of proinflammatory IL-6 cytokine activation in aneurysmal subarachnoid hemorrhage. Neurol Res. 2009 (Epub ahead of print).Google Scholar
- 34.Smith CJ, Emsley HC, Gavin CM, Georgiou RF, Vail A, Barberan EM, et al. Peak plasma interleukin-6, other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity, long-term outcome. BMC Neurol. 2004;4:2.CrossRefPubMedGoogle Scholar