The Course and Clinical Relevance of Interleukin-6 in Cerebrospinal Fluid in Patients with Aneurysmal Subarachnoid Hemorrhage

BACKGROUND: The neuroinflammatory response to aneurysmal subarachnoid hemorrhage (SAH) might have a crucial impact on the burden of disease. We aimed to analyze the behavior of interleukin-6 (IL-6) in cerebrospinal fluid (CSF) during SAH and its relation to complications and outcomes. METHODS: We included consecutive SAH patients with regular CSF IL-6 measurements treated between January 2005 and June 2016 (n = 420). IL-6 levels were recorded every 72 hours (from day 1-3 [d1-3] until day 19-21 [d19-21]). Study endpoints were delayed cerebral infarction (DC-infarction), in-hospital mortality, and unfavorable outcome at 6 months after SAH (modified Rankin scale >3). RESULTS: There was an initial increase of IL-6 on d4-6 (median: 3121 vs. 1467 pg/mL on d1-3), with a gradual decrease over the remaining time. The IL-6 value on d1-3 showed associations with in-hospital mortality and unfavorable outcomes, whereas IL-6 on d4-6 was related to the risk of DC-infarction and in-hospital mortality. According to receiver operating characteristic curves, clinically relevant cutoffs were defined for IL-6 on d1-3 (>2000 pg/mL) and d4-6 (>2500 pg/mL). In multivariate analysis, IL-6 >2000 pg/mL on d1-3 was independently associated with in-hospital mortality (adjusted odds ratio [aOR = 2.67; P = 0.009) and unfavorable outcome (aOR=2.30; P = 0.006). In turn, IL-6 >2500 pg/mL on d4-6 was independently associated with in-hospital mortality (aOR = 2.28; P = 0.017) and DC-infarction (aOR = 1.64; P = 0.044). SAH individuals with angiographic vasospasm showed marked elevation of IL-6 from d1-3 to d4-6 compared to their counterparts without vasospasm (+1770.5 vs. -21 pg/mL; P = 0.02). CONCLUSIONS: Our data confirm the substantial impact of neuroinflammation on SAH. CSF IL-6 values measured during the first week after SAH occurrence present the most valuable outcome predictors.