Plasma Interleukin 6 Levels Predict Long-term Mortality in Aneurysmal Subarachnoid

Abstract

OBJECTIVE: Interleukin 6 (IL-6) is an inflammatory cytokine released into the periphery after stroke, involved in the prognosis of aneurysmal subarachnoid hemorrhage (aSAH). We aimed to explore the relationship between serum IL-6 with long-term mortality after aSAH.METHODS: We retrospectively reviewed the medical records of 18824 SAH patients for collection of serum IL-6 levels during hospitalization from a large, single-center aSAH database of Sichuan University West China Hospital. Patient deaths were determined through a national death record registration system. The primary outcome was long-term mortality. Cox regression models were used to investigate univariate and multivariate relationships between predictors and outcomes. A propensity score-matched analysis was conducted to minimize bias from confounding variables.RESULTS: In total, we included 1131 aSAH patients with 3288 records of IL-6 collections. Initial serum IL-6 values were elevated in all, ranging from 1.50 to 4522.00 pg/ml. After logarithmic transformation, the IL-6 was associated with long-term mortality (HR 1.32, 95% CI 1.21-1.44). The results maintained significant in the multivariate cox regression and propensity score-matched analysis (adjusted HR 1.23, 95% CI 1.11-1.36, p<0.001; IL-6 >103.00 pg/ml vs IL-6≤103. 00 pg/ml, PSM HR 1.94, 95% CI 1.48-2.55, p<0.001). Similar results were observed in the long-term mortality of survivors at discharge and 1-year mortality.CONCLUSIONS: Serum IL-6 is independently associated with long-term mortality of aSAH patients. Our study provided new evidence for the investigation of inflammation after aSAH and the association of inflammatory cytokines with the long-term prognosis of aSAH and might support future management decisions.

A Mini-Review of Magnesium Sulfate's Anti-Inflammatory, Immune, and Neuroprotective Mechanisms in Subarachnoid Hemorrhage

“…In vitro studies have demonstrated that MS can interfere with the nuclear translocation of NF-κB p65 subunit, thereby limiting its transcriptional activity [9]. This mechanism seems to be critical in curbing the production of pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) [10], which are known to be associated with poor prognosis in SAH patients [11,12]. For instance, a retrospective analysis published in 2022 suggested that serum IL-6 peak was independently associated with long-term mortality in a multivariate model evaluating aneurysmal SAH patients [12].…”

“…This mechanism seems to be critical in curbing the production of pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) [10], which are known to be associated with poor prognosis in SAH patients [11,12]. For instance, a retrospective analysis published in 2022 suggested that serum IL-6 peak was independently associated with long-term mortality in a multivariate model evaluating aneurysmal SAH patients [12]. Also, recently, clinical studies have shown a significant reduction in the serum levels of cytokines following the administration of MS [13], indicating a systemic anti-inflammatory action that could be beneficial.…”