Subarachnoid hemorrhage (SAH) induces an inflammatory reaction and may lead to ischemic brain damage. The pathogenesis of brain dysfunction and delayed ischemic symptoms remain difficult to understand despite extensive surveys of such reactions. Cytokine production in the central nervous system following SAH and its relation with clinical outcome have hardly been studied. This study was aimed to determine whether the levels of IL-1 beta, IL-6 and TNF-alpha in the initial cerebrospinal fluid would increase following aneurysmal SAH, and be related with development of delayed ischemic deficit and clinical outcome. Nineteen patients suffering from aneurysmal SAH and 12 control volunteers were the subjects in this study. Cerebrospinal fluid samples were obtained on admission and the levels of each cytokine were determined with enzyme-linked immunosorbent assay. Patients with aneurysmal subarachnoid hemorrhage showed elevated levels of IL-1 beta, and TNF-alpha on admission. The patients with poor neurological status showed high levels of IL-1 beta, and IL-6. The patients who developed delayed ischemic deficit had high level of IL-6. We suggest that elevated level of IL-6 in cerebrospinal fluid of patients with aneurysmal SAH on admission can predict the high risk of delayed ischemic deficit.
Adult ; Aged ; Brain Ischemia/*cerebrospinal fluid/*diagnosis/immunology ; Cytokines/*cerebrospinal fluid ; Female ; Glasgow Outcome Scale ; Human ; Interleukin-1/cerebrospinal fluid ; Interleukin-6/cerebrospinal fluid ; Male ; Middle Age ; Predictive Value of Tests ; Subarachnoid Hemorrhage/*cerebrospinal fluid/*diagnosis/immunology ; Tumor Necrosis Factor/cerebrospinal fluid

PURPOSE: Cytokines found at a inflammatory site may be a good indicator of clinical severity of an infectious inflammatory disease. We assayed interleukin 6 (IL-6) concentrations in cerebrospinal fluid (CSF) from patients affected with viral meningitis, and verified the relationship between IL-6 and inflammatory parameters and whether IL-6 can be used as a diagnostic marker in the diagnosis of viral meningitis. METHODS: We measured CSF IL-6 concentration in viral meningitis (30 cases) and healthy children (3 cases) by using ELISA, and also measured serum and cerebral spinal fluid (CSF) chemistry and inflammatory markers, including C-reactive protein (CRP). We compared the data and analyzed the relationship between the results. RESULTS: The CSF IL-6 levels of viral meningitis (520.1+/-384.3pg/dL) were significantly higher than that of normal control (2.3+/-4.0pg/dL) (P<0.05). The relationship between CSF IL-6 level and serum CRP was significant (P=0.0041). The relationship between CSF protein level and CSF IL-6 level was significant (P=0.001). There was no significant correlation between CSF IL-6 level and CSF WBC count. CONCLUSION: According to these results, we concluded that viral meningitis is highly associated with CSF IL-6, and we predict CSF IL-6 is useful in the diagnosis and prediction of treatment for viral meningitis.
C-Reactive Protein ; Cerebrospinal Fluid* ; Chemistry ; Child ; Cytokines ; Diagnosis ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-6* ; Meningitis, Viral*

OBJECTIVE: Magnetic resonance imaging (MRI) of chronic subdural hematoma (CSDH) detects various patterns, which can be attributed to many factors. The purpose of this study was to measure the level of interleukin-6 (IL-6), interleukin-8 (IL-8), and highly specific protein [beta-trace protein (betaTP)] for cerebrospinal fluid (CSF) in CSDHs, and correlate the levels of these markers with the MRI findings. METHODS: Thirty one patients, treated surgically for CSDH, were divided on the basis of MRI findings into hyperintense and non-hyperintense groups. The concentrations of IL-6, IL-8, and betaTP in the subdural fluid and serum were measured. The betaTP was considered to indicate an admixture of CSF to the subdural fluid if betaTP in the subdural fluid (betaTP(SF))/betaTP in the serum (betaTP(SER))>2. RESULTS: The mean concentrations of IL-6 and IL-8 of the hyperintense group (n=17) of T1-WI MRI were 3975.1+/-1040.8 pg/mL and 6873.2+/-6365.4 pg/mL, whereas them of the non-hyperintense group (n=14) were 2173.5+/-1042.1 pg/mL and 2851.2+/-6267.5 pg/mL (p<0.001 and p=0.004). The mean concentrations of betaTP(SF) and the ratio of betaTP(SF)/betaTP(SER) of the hyperintense group (n=13) of T2-WI MRI were 7.3+/-2.9 mg/L and 12.6+/-5.4, whereas them of the non-hyperintense group (n=18) were 4.3+/-2.3 mg/L and 7.5+/-3.9 (p=0.011 and p=0.011). CONCLUSION: The hyperintense group on T1-WI MRI of CSDHs exhibited higher concentrations of IL-6 and IL-8 than non-hyperintense group. And, the hyperintese group on T2-WI MRI exhibited higher concentrations of betaTP(SF) and the ratio of betaTP(SF)/betaTP(SER) than non-hyperintense group. These findings appear to be associated with rebleeding and CSF admixture in the CSDHs.
Cerebrospinal Fluid ; Cytokines* ; Hematoma, Subdural, Chronic* ; Humans ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Magnetic Resonance Imaging* ; Prospective Studies*

OBJECTIVETo study the antipyretic effect of baicalin in inhibiting yeast-induced fever in rats and the influence on inflammatory cytokine, then explore the possible mechanism of baicalin in inhibiting yeast-induced fever in rats.

METHODSRat modles of pyrexia were established by subcutaneous injection of yeast (2 g x kg(-1)); the rats of were divided into the normal control, model, baicalin high, medium and low-dose group and the effect of baicalin on the changes of the rats' temperature were observed. Dual antibody ELISA method was used to test the changes of IL-6, IL-1beta and TNF-alpha contents in in serum , hypothalamus and cerebral spinal fluid (CSF). Then analyze the correlation between the inhibition ratio of temperature heighten on three different dose of baicalin and the inhibition ratio of the contents heighten on IL-6, IL-1beta and TNF-alpha.

RESULTThe high dose of baicalin significantly inhibited the yeast-induced fever of rats, and decresesed IL-6, IL-1beta and TNF-alpha contents in serum, hypothalamus and CSF. The inhibition ratio of temperature heighten of baicalin had direct correlation with the inhibition ratio of the heighten on IL-1beta content in serum, hypothalamus and CSF (r = 0.873, P < 0.05), also dose TNF-alpha (r = 0.862, P < 0.01).

CONCLUSIONBaicalin may have obvious antipyretic effect by decreasing the increasing contents of IL-1beta and TNF-alpha in rats.

Animals ; Body Temperature ; drug effects ; Cytokines ; blood ; cerebrospinal fluid ; metabolism ; Fever ; blood ; cerebrospinal fluid ; drug therapy ; physiopathology ; Flavonoids ; pharmacology ; therapeutic use ; Hypothalamus ; drug effects ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Time Factors

PURPOSE: Cytokines play important roles on the expression of various neuronal inflammatory disease and insults. The purpose of this study was to evaluate the levels of interleukine (IL)-6, IL-8, IL-10 in cerebrospinal fluid (CSF) in children with aseptic meningitis and compare them with those of the patients having other acute neurological symptoms. METHODS: We retrospectively reviewed the medical records of the children who admitted in the pediatric department of Hanyang University Guri Hospital for acute neurological symptoms and had CSF examinations from September 2012 to July 2013. We classified them into six groups as acute encephalopathy, epilepsy, febrile convulsion, headache, infantile fever, and meningitis. We analyzed the clinical and laboratory data from them. RESULTS: A total of 87 CSFs of the patients were available. The levels of CSF IL-6, IL-8, and IL-10 were significantly increased in the group with aseptic meningitis group as compared to the other groups (P<0.05). CSF IL-6 (r=0.576, P=0.000), IL-8 (r=0.329, P=0.003), and IL-10 (r=0.523, P=0.000) were all significantly correlated with CSF White bood cell (WBC) count. Among the patients with aseptic meningitis, CSF enterovirus positive patients (CSF entero+) showed significantly increased IL-6, IL-8, IL-10 levels than CSF enterovirus negative patients (CSF entero-) (P<0.05). In addition, the CSF entero+ and the increase of IL-10 were significantly correlated (x2=6.827, P=0.033). CONCLUSION: In patients with aseptic meningitis, the CSF IL-6, IL-8 and IL-10 were more expressed than in other neurological disease group. Among them, the enteroviral meningitis may be more related with IL-6, IL-8 and IL-10 expression than in other causes of aseptic meningitis.
Cerebrospinal Fluid* ; Child* ; Cytokines ; Enterovirus ; Epilepsy ; Fever ; Headache ; Humans ; Interleukin-10 ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Medical Records ; Meningitis ; Meningitis, Aseptic* ; Neurons ; Retrospective Studies ; Seizures, Febrile

This study was conducted to determine the level of inflammatory cytokines in the cerebrospinal fluid (CSF) of patients with meningitis. All the CSF of the patients were examined by Gram and acid-fast stain, culture, and PCR for Mycobacterium tuberculosis and Mycoplasrma spp..The levels of sugar, protein and leukocytes count were also evaluated in the CSFs. Concentrations of Interleukin (IL)-1B, IL-6, IL-8, tumor necrosis factor (TNF)-a in the CSF were evaluated by the ELISA kit (Genzyme, USA). General bacteria, tubercle bacilli, and Mycoplasma spp. were not detected with stain and culture methods, but, Mycoplasma spp. was detected by PCR method from four (6.3%) patients with meningitis. The mean CSF concentration of IL-1B, IL-6, IL-8, and TNF-cx in the control group were 0.6+/-0.2, 896.8+/-107.6, 50.1+/-5.1, and 4.8+/-1.4 pg/ml, respectively. The mean CSF concentration of IL-1B, IL-6, IL-8, and TNF-a in the patients with aseptic meningitis were 3.8+/-0.6, 1261.6+/-144.3, 466.7+/-42.3, and 10.8+/-2.0 pg/ml, respectively. The mean CSF concentration of IL-1B, IL-6, IL-8, and TNF-a in the patients with mycoplasmal meningitis were 10.2+/-8.1, 1979.5+/-133.8, 459.7+/-96.4, and 17.5+/-5.1 pg/ml, respectively. There were significantly differences in the levels of IL-1B, IL-6, IL-8, and TNF-a between control and patients with aseptic meningitis or Mycoplasmal meningitis (each p<0.001). These results suggest that increased levels of IL-1B, IL-8, and TNF-a could be higly suggestive of meningitis.
Bacteria ; Cerebrospinal Fluid* ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-6* ; Interleukin-8* ; Interleukins ; Leukocytes ; Meningitis* ; Meningitis, Aseptic ; Mycobacterium tuberculosis ; Mycoplasma ; Polymerase Chain Reaction ; Tumor Necrosis Factor-alpha

BACKGROUND AND OBJECTIVES: Cytokines such as interleukin-1beta (IL-1beta) released into cerebrospinal fluid (CSF) during bacterial meningitis play an important role in causing inflammation and tissue damage. Bacterial meningitis is often complicated by a sensorineural hearing loss. The present study is to investigate the effect of IL-1beta injected into CSF on hearing in guinea pigs. MATERIALS AND METHODS: Thirty guinea pigs (60 ears) were randomly assigned to the following three groups: 1) Control group receiving intracisternal PBS injection. 2) 10 ng group receiving intracisternal injection of 10 ng/ml of IL-1beta. 3) 100 ng group receiving intracisternal injection of 100 ng/ml of IL-1beta. Auditory brainstem response (ABR) was performed before the injection, 10, and 24 hours after the injection of PBS and IL-1beta. The concentration of IL-1beta in the perilymph was measured in each group. RESULT: The ABR threshold shift at 10 and 24 hours were respectively 3.3+/-2.6 dB, 2.8+/-2.0 dB in the control group, 21.94+/-14.46 dB, 5.83+/-9.74 dB in the 10 ng group, and 21.58+/-15.99 dB, 4.74+/-9.05 dB in the 100 ng group. The ABR thresholds were significantly increased in the 10 and 100 ng groups compared to the control group at 10 hours, but they were not significantly different at 24 hours after the injection. The concentrations of IL-1beta in the perilymph at 10 hours were 2.17+/-0.6 ng/ml in the 10 ng group and 3.58+/-1.1 ng/m in the 100 ng group. Those were 0.53+/-0.1 ng/ml in the 10 ng and 0.86+/-0.2 ng/ml in the 100 ng groups at 24 hours after the injection. CONCLUSION: The results of this study showed that IL-1beta released into CSF during meningitis may play an important role in causing hearing loss.
Animals ; Cerebrospinal Fluid* ; Cytokines ; Evoked Potentials, Auditory, Brain Stem ; Guinea Pigs* ; Guinea* ; Hearing Loss ; Hearing Loss, Sensorineural ; Hearing* ; Inflammation ; Interleukin-1beta ; Meningitis ; Meningitis, Bacterial ; Perilymph

Severe intraventricular hemorrhaging (IVH) in premature infants and subsequent posthemorrhagic hydrocephalus (PHH) causes significant mortality and life-long neurological complications, including seizures, cerebral palsy, and developmental retardation. However, there are currently no effective therapies for neonatal IVH. The pathogenesis of PHH has been mainly explained by inflammation within the subarachnoid spaces due to the hemolysis of extravasated blood after IVH. Obliterative arachnoiditis, induced by inflammatory responses, impairs cerebrospinal fluid (CSF) resorption and subsequently leads to the development of PHH with ensuing brain damage. Increasing evidence has demonstrated potent immunomodulating abilities of mesenchymal stem cells (MSCs) in various brain injury models. Recent reports of MSC transplantation in an IVH model of newborn rats demonstrated that intraventricular transplantation of MSCs downregulated the inflammatory cytokines in CSF and attenuated progressive PHH. In addition, MSC transplantation mitigated the brain damages that ensue after IVH and PHH, including reactive gliosis, cell death, delayed myelination, and impaired behavioral functions. These findings suggest that MSCs are promising therapeutic agents for neuroprotection in preterm infants with severe IVH.
Animals ; Arachnoid ; Arachnoiditis ; Brain ; Brain Injuries ; Cell Death ; Cell Transplantation ; Cerebral Palsy ; Cerebrospinal Fluid ; Cytokines ; Gliosis ; Hemolysis ; Hemorrhage* ; Humans ; Hydrocephalus ; Infant, Newborn ; Infant, Premature* ; Inflammation ; Intracranial Hemorrhages ; Mesenchymal Stromal Cells* ; Mortality ; Myelin Sheath ; Rats ; Seizures ; Subarachnoid Space

The aim of this study is to investigate the effect of (S)-4-carboxy-3-hydroxy-phenylglycine [(S)-4C3HPG], a mixed group I glutamate metabotropic receptor antagonist and a group II agonist, on impairment in a cortical impact model of traumatic brain injury (TBI) in mice and to elucidate the possible mechanisms. Mice were injected (i.p.) with saline, 1 mg/kg (S)-4C3HPG, 5 mg/kg (S)-4C3HPG and 10 mg/kg (S)-4C3HPG (n=10 per group), respectively, at 30 min before moderate TBI. Neurological deficit scores, water content in injured brain and glutamate concentration in cerebral spinal fluid (CSF) were detected at 24 h after TBI. The expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) mRNA in injured cortex were also detected by real-time RT-PCR. The results showed that the neurological deficits and cerebral edema were significantly attenuated in mice pretreated with (S)-4C3HPG (5 and 10 mg/kg respectively) compared with those in mice pretreated with saline. Furthermore, (S)-4C3HPG treatment also decreased the glutamate concentration in CSF and the expressions of TNF-α and IL-1β mRNA remarkably in a dose-dependent manner. These results suggest that (S)-4C3HPG treatment attenuates cortical impact-induced brain injury possibly via suppression of glutamate release and inhibition of excessive inflammatory cytokine production. These findings highlight the potential benefit of glutamate metabotropic receptor ligand for preventing TBI.
Animals ; Brain Injuries ; drug therapy ; metabolism ; physiopathology ; Cytokines ; metabolism ; Glutamic Acid ; cerebrospinal fluid ; Glycine ; analogs & derivatives ; therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Receptors, Metabotropic Glutamate ; agonists ; antagonists & inhibitors

BACKGROUND AND PURPOSE: A few groups have suggested that activated cytokines and nitrosative stress are closely involved in the pathogenesis of different demyelinating disorders induced by the neuroinflammatory destruction of neurons. The purpose of this study was to elucidate the associations of cytokines and S-nitrosothiols (RSNO) with the severity of neurodegeneration during relapse in demyelinating disorders of the central nervous system. METHODS: We measured levels of interleukin-6 (IL-6), erythropoietin, RSNO, and phosphorylated neurofilament heavy chain (pNfh) in cerebrospinal fluid (CSF) samples obtained from patients with different demyelinating disorders: multiple sclerosis (MS, n=52), acute disseminated encephalomyelitis (ADEM, n=9), and neuromyelitis optica spectrum disorders (NMOSD) with aquaporin-4 immunoglobulin G (AQP4-IgG, n=12). We compared these levels with those measured in a control group (n=24). RESULTS: We found that IL-6 in CSF was elevated in NMOSD with AQP4-IgG and ADEM patients as well as in MS patients after the destruction of soluble IL-6. Erythropoietin levels were lower in MS, while RSNO levels were higher in NMOSD with AQP4-IgG and MS patients than in the control group. CSF pNfh levels were elevated in MS and ADEM patients. CONCLUSIONS: These results confirm that IL-6 is activated in different demyelinating disorders, with this elevation being more prominent in the CSF of NMOSD with AQP4-IgG and ADEM patients. Moreover, S-nitrosylation is activated in demyelinating disorders with spinal-cord injury and neurodegeneration in these patients. However, we found no correlation between these biochemical markers, and so we could not confirm whether IL-6-mediated nitric oxide production is involved in spinal-cord lesions.
Biomarkers ; Central Nervous System* ; Cerebrospinal Fluid ; Cytokines ; Demyelinating Diseases* ; Encephalomyelitis, Acute Disseminated ; Erythropoietin ; Humans ; Immunoglobulin G ; Interleukin-6* ; Intermediate Filaments ; Multiple Sclerosis ; Neuromyelitis Optica ; Neurons ; Nitric Oxide ; Recurrence ; S-Nitrosothiols*