interleukin-8 and Subarachnoid-Hemorrhage

To investigate the relationship between the dynamic changes of pro-inflammatory cytokines in cerebrospinal fluid (CSF) and headache in patients with aneurysmal subarachnoid hemorrhage (aSAH)at hospital admission.. CSF was collected from patients with aSAH at four time points (days 1, 3, 5, and 7; n = 216) from January 2017 to August 2017 at the Department of Neurosurgery of the First Affiliated Hospital of Wannan Medical College. We measured CSF levels ofinterleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α) levels using an enzyme-linked immunosorbent assay. Results were statistically analyzed to determine the relationship between the dynamic changes of pro-inflammatory cytokines in CSF and headache after aSAH.. The concentrations of IL-1β, IL-6, IL-8, and TNF-α in CSF showed dynamic changes after aSAH. Spearman correlation coefficient analysis revealed that high Hunt-hess grade and modified Fisher scale were associated with a worse headache after aSAH on days 1 and 7 (all P < 0.05). High values of intracranial pressure (ICP) and high levels of CSF pro-inflammatory cytokines were associated with a worse headache after aSAH at four time points (all P < 0.05). However, no significant associations were found between headache and sex, and age. After multiple regression analysis, the Hunt-hess grade, the levels of IL-6 and the levels of TNF-α were associated with headache severity at day 1 (all P < 0.05). The ICP, the levels of IL-1β and the levels of TNF-α were associated with headache severity on day 3, 5 and 7 (all P < 0.05).. Pro-inflammatory cytokines in CSF are closely associated with a headache after aSAH, and therefore may be a therapeutic target in the future.

Topics: Biomarkers; Cytokines; Headache; Humans; Interleukin-6; Interleukin-8; Subarachnoid Hemorrhage; Tumor Necrosis Factor-alpha

Inflammation is closely associated with prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH), which is orchestrated by inflammatory cytokines. Therefore, this study aimed to investigate the levels of inflammatory cytokines in the early stage of aSAH and their predictive value for prognosis.. In this retrospective study, 206 patients with aSAH were recruited and assigned to a severe group (WFNS grade ≥ 4) and a mild group (WFNS grade < 4) according to the severity of patients on admission. Flow cytometry was performed to detect the levels of 12 inflammatory cytokines in the serum of patients. Then, patients were grouped into a poor prognosis group (mRS score ≥ 4) and a good prognosis group (mRS score < 4) based on their prognosis after 3 months of discharge to compare the relationship between cytokines and prognosis. Propensity score matching (PSM) was utilized to control confounding factors. The correlation between inflammatory factors and prognosis was determined using Spearman correlation, and the predictive efficacy of inflammatory factors was tested by a receiver operating characteristic curve.. Serum IL-1β, IL-5, IL-6, IL-8, IL-10, IFN-γ, and TNF-α levels were significantly higher in the mild group than in the severe group and in the poor prognosis group than in the good prognosis group. After PSM, the differences in IL-1β, IL-5, IFN-α, and IFN-γ levels disappeared between the two groups, whereas IL-2, IL-6, IL-8, IL-10, and TNF-α levels remained higher in the poor prognosis group than in the good prognosis group. Additionally, IL-2, IL-6, IL-8, and IL-10 levels were positively correlated with mRS scores. Moreover, the predictive value was found to be the highest for IL-6 and the lowest for TNF-α.. Inflammation degree was related to the severity of aSAH. Inflammatory markers, including IL-6, IL-10, IL-8, IL-2, and TNF-α, might predict the poor prognosis of aSAH.

Topics: Cytokines; Humans; Inflammation; Interleukin-10; Interleukin-2; Interleukin-5; Interleukin-6; Interleukin-8; Retrospective Studies; Subarachnoid Hemorrhage; Tumor Necrosis Factor-alpha

High-mobility group box 1 protein (HMGB1) is a nuclear factor that is a potent proinflammatory mediator, and may trigger increases in other inflammatory cytokines. The inflammatory cytokines in the cerebrospinal fluid (CSF) of patients with subarachnoid hemorrhage (SAH) have been reported previously, but HMGB1 has not. In this study, we measured HMGB1 and the inflammatory cytokines in the CSF of patients with SAH.. CSF samples were collected on days 3, 7, and 14 from the drainage tubes of the postaneurysm clips of 39 patients with SAH. HMGB1, interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNF-alpha) were measured in the CSF, and compared between the patients with favorable (good recovery and moderate disability) and unfavorable outcomes (severe disability, vegetative state, and death) at 3 months.. In the unfavorable outcome group, HMGB1 (P = 0.017), IL-6 (P = 0.003), IL-8 (P = 0.041), and TNF-alpha (P = 0.002) were significantly increased. HMGB1 correlated significantly with IL-6, IL-8, and TNF-alpha (R = 0.672, 0.421, and 0.697, respectively).. HMGB1 was increased in the CSF of SAH patients with an unfavorable outcome, as were the other cytokines. These results suggest that HMGB1 and cytokines are related to the brain damage observed after SAH. HMGB1 might play a key role in the inflammatory response in the CNS of SAH patients.

Topics: Aged; Encephalitis; Female; Glasgow Coma Scale; HMGB1 Protein; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Recovery of Function; Subarachnoid Hemorrhage; Tumor Necrosis Factor-alpha

To study the expression change of interleukin-8 (IL-8) gene in the basilar artery of rabbit and the effect of IL-8 on the development of cerebral vasospasm induced by experimental subarachnoid hemorrhage (SAH).. Thirty five healthy Japanese White Rabbits were randomly divided into saline-control group and experimental group. The experimental group was subdivided into four groups, representing day 1, 4, 7 and 14 after the first blood injection of SAH. The delayed cerebral vasospasm (DCVS) model was established by double injection of autologous blood into the cisterna magna. The expression change of cytokine IL-8 mRNA in the basilar artery was analyzed by RTPCR.. The expression of IL-8 gene increased on day 4-7 after the first blood injection of SAH compared with control (P< 0.001), and decreased to normal on day 14. The expression of IL-8 gene in the SAH groups were positively correlated with the degree of basilar artery stenosis (r = 0.642, P< 0.01).. The expression level of IL-8 gene in basilar arteries was intimately associated with the degree of cerebral vasospasm, suggesting that IL-8 may play an important role in the DCVS after SAH as an immunological inflammatory factor.

Topics: Animals; Basilar Artery; Disease Models, Animal; Gene Expression Regulation; Interleukin-8; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Subarachnoid Hemorrhage; Time Factors

Several studies reported that the levels of proinflammatory cytokines such as TNF-alpha, IL-1beta, IL-6, and IL-8 are elevated in the cerebrospinal fluid (CSF) of patients after subarachnoid hemorrhage (SAH). Cytokines in CSF may contribute to the development of vasospasm and cerebral ischemia. In the present study, we investigated the possible cytotoxic effects of these cytokines on cultured cerebral microvascular endothelial cells.. The effects of TNF-alpha, IL-1beta, IL-6, and IL-8 were tested using cell viability assay, DNA fragmentation analysis (DNA laddering), Western blot analysis (Anti-poly-(ADP-ribose) polymerase [PARP] antibody), and caspase-3 activity.. TNF-alpha and IL-1beta, but not IL-6 or IL-8, caused cell detachment in a dose-dependent manner (p<0.05). TNF-alpha (200 pg/ml) and IL-1beta (150 pg/ml) produced DNA ladders at 24-72 h. TNF-alpha but not IL-1beta cleaved the PARP from 116- to 85-kDa fragments and enhanced caspase-3 activity at 24-72 h after incubation with endothelial cells. Caspase-3 inhibitor at 10 micromol/l significantly prevented TNF-alpha-induced cell detachment (p<0.05).. TNF-alpha induces apoptosis in cultured cerebral endothelial cells through the cleavage of caspase-3. IL-1beta decreases the adherent cells, produces DNA ladders, but fails to cleave PARP or increase caspase-3 activity. IL-1beta may induce apoptosis in cerebral endothelial cells through different pathway from that of TNF-alpha.

Topics: Animals; Blotting, Western; Capillaries; Caspase 3; Caspase Inhibitors; Caspases; Cattle; Cell Count; Cell Line; Cell Survival; Cerebrovascular Circulation; Cytokines; DNA Fragmentation; Endothelial Cells; Enzyme Inhibitors; Interleukin-1; Interleukin-6; Interleukin-8; Poly(ADP-ribose) Polymerases; Subarachnoid Hemorrhage; Tumor Necrosis Factor-alpha

Cytokines are considered as mediators of immune and inflammatory responses. Cisternal CSF levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and of the soluble adhesion molecule E-selectin were evaluated in patients operated on for intracranial aneurysms. Cisternal CSF samples were obtained at surgery in 41 selected patients (31 with diagnosis of subarachnoid hemorrhage (SAH) and 10 control patients operated on for incidental unruptured aneurysms); 14 patients were operated within 72 h after SAH (early surgery) and 17 were operated after day 10 after the hemorrhage (delayed surgery). The CSF levels of cytokines were evaluated using radioimmunoassay and their concentrations were related to the timing of surgery, the amount of cisternal subarachnoid blood clots and the onset of clinical and angiographical evidence of arterial vasospasm. Mean cisternal CSF levels of IL-6, IL-8 and AMCP-1 are significantly higher in samples obtained from patients early operated after SAH, while levels of E-selectin were below the threshold value of the method in all 41 cases. In the early operated group 7 patients presented symptomatic vasospasm: levels of IL-8 and MCP-1 were not significantly different were compared to those of uncomplicated cases; on the other hand, significantly higher levels of IL-6 were shown in the subgroup of patients operated within 72 h after SAH and developing vasospasm. Among the patients undergoing delayed surgery 5 presented symptomatic vasospasm, but no significant difference was shown in cisternal CSF levels of cytokines measured. The results of the present study show that in patients with unruptured aneurysms cytokines are present in cisternal CSF in scarce quantities and that in subarachnoid spaces after SAH there is an impressive increase of IL-6, IL-8 and MCP-1. Moreover, the higher cisternal CSF levels of IL-6 found in the early stage after SAH might have a predictive value regarding the occurrence of symptomatic vasospasm.

Topics: Chemokine CCL2; Cisterna Magna; Cytokines; E-Selectin; Female; Humans; Interleukin-6; Interleukin-8; Intracranial Aneurysm; Ischemic Attack, Transient; Male; Middle Aged; Subarachnoid Hemorrhage

Inducible cyclooxygenase (COX-2) has been found to play a pathological role in cerebral insult. We investigated the expression of COX-2 in the basilar artery after experimental subarachnoid hemorrhage (SAH).. In a canine "two-hemorrhage" model of SAH, the basilar arteries were obtained on day 2 after a cisternal injection of autologous blood or on days 4, 6, 7, or 9 after the second injection. Basilar arteries also were obtained 12 hours after intracisternal injection a cytokine: interleukin (IL)-1 beta (0.03 microgram), IL-6 (3 micrograms), or IL-8 (10 micrograms). Western blotting with a polyclonal anti-COX-2 antibody was performed in these arteries.. COX-2 protein was not demonstrated in the basilar artery in control animals without SAH. However, it was expressed in the basilar artery on days 2, 4, 6, and 7 after blood injection but not on day 9. Intracisternal injection of IL-1 beta, IL-6, or IL-8 also induced COX-2 in the basilar artery.. COX-2 expression was detected in basilar arterial tissue in both acute and chronic stages after SAH. Elevation of inflammatory cytokines after SAH may be involved in the induction of COX-2, which may produce sufficient quantities of eicosanoids to affect hemodynamics after SAH.

Topics: Animals; Basilar Artery; Blotting, Western; Cerebral Angiography; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Dogs; Enzyme Induction; Female; Injections, Intraventricular; Interleukin-1; Interleukin-6; Interleukin-8; Isoenzymes; Male; Peroxidases; Prostaglandin-Endoperoxide Synthases; Subarachnoid Hemorrhage

The authors characterized the role of interleukins in the cerebrospinal fluid (CSF) in the development of vasospasm after subarachnoid haemorrhage (SAH), particularly interleukin-6 (IL-6). Concentrations of interleukin-1 beta (IL-1 beta), IL-6, and interleukin-8 (IL-8) were measured serially in CSF of 24 patients and in serum of 9 patients with SAH and correlated clinically. Additionally, the effects of the same cytokines on the cerebral arteries of dogs were analyzed on angiograms after intracisternal injection. Changes in levels of eicosanoids, angiogenic factors, and soluble cell adhesion molecules were investigated in the CSF of injected dogs. CSF concentrations of IL-6 and IL-8 were elevated significantly above control levels from the acute stage of SAH until the chronic stage. Patients with symptomatic vasospasm had significantly higher levels of IL-6 as well as IL-8 in CSF on days 5 and 7. Intracisternal injection of IL-6 induced long-lasting vasoconstriction in five out of eight dogs, while IL-8 did not. The diameter of canine basilar artery after IL-6 was reduced 29 +/- 5% from pretreatment diameter at 8 hours. Prostaglandins E2 and I2 were elevated in CSF for the first 4.5 hour of this IL-6-induced vasospasm. Neither angiogenic factors such as platelet-derived growth factor-AB and vascular endothelial growth factor nor soluble cell adhesion molecules were significantly elevated in CSF. IL-6, which increases to very high concentrations in CSF after SAH, may be important in inducing vasospasm, as IL-6 produced long-lasting vasoconstriction in the canine cerebral artery, which may be partly related to activation of the prostaglandin cascade.

Topics: Animals; Cerebral Arteries; Dogs; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Ischemic Attack, Transient; Male; Middle Aged; Reference Values; Subarachnoid Hemorrhage; Vasoconstriction

After acute brain injury there may be increased intracranial production of cytokines, with activation of inflammatory cascades. We have sought to determine if a transcranial cytokine gradient was demonstrable in paired sera of 32 patients requiring intensive care after acute brain injury. The difference between concentrations of IL-1 beta, IL-6, IL-8 and TNF alpha in jugular venous and arterial serum was measured on admission, and at 24, 48 and 96 h after the primary injury. There were no differences in IL-1 beta, IL-8 or TNF alpha, but median gradients of 6.7 and 11.5 pg ml-1 for IL-6 were demonstrated in the traumatic brain injury (n = 22) and subarachnoid haemorrhage (n = 10) groups, respectively (normal values in serum < 4.7 pg ml-1; P < 0.001 both groups). This suggests that there is significant production of IL-6 by intracranial cells after acute brain injury. Therapy directed towards combatting the negative effects of IL-6 may potentially benefit patients who have sustained an acute brain injury.

Topics: Acute Disease; Adolescent; Adult; Aged; Brain; Brain Injuries; Critical Care; Cytokines; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Jugular Veins; Male; Middle Aged; Subarachnoid Hemorrhage; Tumor Necrosis Factor-alpha

Pathophysiological mechanisms for vasospasm after subarachnoid haemorrhage (SAH) remain unclear and, so far, roles of cytokines in vasospasm have not been known. In the present study, we measured interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour necrosis factor-alpha (TNF-alpha) concentrations in the cerebrospinal fluid (CSF) of patients with subarachnoid haemorrhage (SAH). ELISA assay were performed on 21 CSF samples from 7 patients with SAH and on 4 sera samples. Both IL-6 and IL-8 were detected in all CSF samples, but IL-1 alpha, IL-1 beta, and TNF-alpha were not detected. IL-6 and IL-8 were also detected in sera, but at much lower concentrations. This study indicates that IL-6 and IL-8 may play roles as immunomodulators in patients with SAH. In addition, it has been reported that IL-6 inhibits prostaglandin I2 production and increases the mRNA level of c-sis gene, suggesting that IL-6 may play an important role in vasospasm as vasoconstrictor.

Topics: Aged; Cytokines; Endothelium; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Subarachnoid Hemorrhage; Vasoconstriction