title: Elevated IL-6 and TNF-α Levels in Cerebrospinal Fluid of Subarachnoid Hemorrhage Patients.
abstract: The present study investigated the correlation between interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels in cerebrospinal fluid (CSF) and subarachnoid hemorrhage (SAH) progression. A meta-analysis was further conducted from pooled data to analyze the clinical value of IL-6 and TNF-α in SAH diagnosis. In our case-control study, a total of 57 SAH patients were assigned to two groups, CVS group (n = 27) and non-CVS group (n = 30), based on the presence of cerebral vasospasm (CVS). In addition, 65 healthy subjects were enrolled as controls. IL-6 and TNF-α levels in CSF were measured in all the study subjects by enzyme-linked immunosorbent assay (ELISA). For meta-analysis, an exhaustive literature search was conducted to identify relevant published articles and strict inclusion and exclusion criteria were applied to select studies for the present meta-analysis. Data extracted from these studies was analyzed using STATA 12.0 software. IL-6 and TNF-α levels in CSF of SAH patients were markedly higher than those of healthy controls (all P < 0.001). Further, CVS patients showed elevated IL-6 and TNF-α levels in CSF compared to non-CVS patients (all P < 0.001). The increase in IL-6 and TNF-α levels in CSF correlated with the increasing disease severity, based on Hunt-Hess grade, in SAH patients (all P < 0.05). Our meta-analysis also confirmed that IL-6 and TNF-α CSF levels were markedly higher in SAH patients compared to healthy controls (all P < 0.001). Ethnicity-stratified analysis showed that both IL-6 and TNF-α CSF levels were elevated in Asian SAH patients, compared to their healthy counterparts (all P < 0.05). The TNF-α CSF levels were significantly higher in Caucasian SAH patients (P < 0.001), but the IL-6 CSF levels showed no such differences compared to the healthy controls (P = 0.219). Subgroup analysis based on the presence of CVS showed that both IL-6 and TNF-α CSF levels were markedly higher in CVS patients than those in non-CVS patients (all P < 0.05). Our results provide strong evidence that IL-6 and TNF-α CSF levels are elevated in SAH patients and may participate in SAH development. Thus, these two cytokines could be important biomarkers for early diagnosis and disease monitoring in SAH patients.
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, No 71 Xinmin Street, Changchun, 130021, Jilin Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, No 71 Xinmin Street, Changchun, 130021, Jilin Province, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, No 71 Xinmin Street, Changchun, 130021, Jilin Province, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, China.
authors.forename: Xi-Jia
authors.initials: XJ
authors.lastname: Fu
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, No 71 Xinmin Street, Changchun, 130021, Jilin Province, China.
authors.forename: Tie-Zhu
authors.initials: TZ
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, No 71 Xinmin Street, Changchun, 130021, Jilin Province, China.
authors.forename: Yue-Ting
authors.initials: YT
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, No 71 Xinmin Street, Changchun, 130021, Jilin Province, China.
authors.forename: Xin-Liang
authors.initials: XL
authors.lastname: Ren
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, No 71 Xinmin Street, Changchun, 130021, Jilin Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, No 71 Xinmin Street, Changchun, 130021, Jilin Province, China.
authors.forename: Han-Rui
authors.initials: HR
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, No 71 Xinmin Street, Changchun, 130021, Jilin Province, China. liyunqianlyq555@126.com.
authors.forename: Yun-Qian
authors.initials: YQ
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005006:Ethnicity; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid* / Q000150:complications / Q000000981:diagnostic imaging; D014057:Tomography, X-Ray Computed; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid*; D020301:Vasospasm, Intracranial / Q000134:cerebrospinal fluid / Q000150:complications / Q000000981:diagnostic imaging
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
keywords: Case-control study; Cerebral vasospasm; Cerebrospinal fluid; Correlation; IL-6; Meta-analysis; Subarachnoid hemorrhage; TNF-α