interleukin-8 and Cerebral-Hemorrhage

Intracerebral hemorrhage (ICH) is a severe neurological disorder with no proven treatment. Inflammation after ICH contributes to clinical outcomes, but the relevant molecular mechanisms remain poorly understood. In studies of peripheral leukocyte counts and mRNA-sequencing (mRNA-seq), our group previously reported that monocytes and Interleukin-8 (IL-8) were important contributors to post-ICH inflammation. microRNA (miRNA) are powerful regulators of gene expression and promising therapeutic targets. We now report findings from an integrated analysis of miRNA-seq and mRNA-seq in peripheral blood mononuclear cells (PBMCs) from a swine ICH model. In 10 pigs, one PBMC sample was collected immediately prior to ICH induction and a second 6 h later; miRNA-seq and mRNA-seq were completed for each sample. An aggregate score calculation determined which miRNA regulated the differentially expressed mRNA. Networks of molecular interactions were generated for the combined miRNA/target mRNA. A total of 227 miRNA were identified, and 46 were differentially expressed after ICH (FDR < 0.05). The anti-inflammatory miR-181a was decreased post-ICH, and it was the most highly connected miRNA in the miRNA/mRNA bioinformatic network analysis. miR-181a has interconnected pathophysiology with IL-8 and monocytes; in prior studies, we found that IL-8 and monocytes contributed to post-ICH inflammation and ICH clinical outcome, respectively. miR-181a was a significant mediator of post-ICH inflammation and is promising for further study, including as a potential therapeutic target. This investigation also demonstrated feasible methodology for miRNA-seq/mRNA-seq analysis in swine that is innovative, and with unique challenges, compared with transcriptomics research in more established species.

Topics: Animals; Cerebral Hemorrhage; Female; Interleukin-8; Leukocytes, Mononuclear; MicroRNAs; RNA, Messenger; Swine; Transcriptome

Topics: Adult; Aged; Cerebral Hemorrhage; Female; Gene Expression Profiling; Humans; Inflammation; Interleukin-8; Male; Middle Aged; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; NF-kappa B; Transcriptome

To see if the systemic inflammation profile of 123 infants born before the 28th week of gestation who had intraventricular hemorrhage without white matter injury differed from that of 68 peers who had both lesions, we compared both groups to 677 peers who had neither. Cranial ultrasound scans were read independently by multiple readers until concordance. The concentrations of 25 proteins were measured with multiplex arrays using an electrochemiluminescence system. Infants who had both hemorrhage and white matter injury were more likely than others to have elevated concentrations of C-reactive protein and interleukin 8 on days 1, 7, and 14, and elevated concentrations of serum amyloid A and tumor necrosis factor-α on 2 of these days. Intraventricular hemorrhage should probably be viewed as 2 entities: hemorrhage alone and hemorrhage with white matter injury. Each entity is associated with inflammation, but the combination has a stronger inflammatory signal than hemorrhage alone.

Topics: Age Factors; C-Reactive Protein; Cerebral Hemorrhage; Female; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Inflammation; Interleukin-8; Leukoencephalopathies; Male; Odds Ratio; Serum Amyloid A Protein; Tumor Necrosis Factor-alpha; Ultrasonography, Doppler

Spontaneous intracerebral hemorrhage (ICH) represents about 15% of all strokes and is associated with high mortality rates. Our aim was to identify the gene expression changes and biological pathways altered in the brain following ICH.. Twelve brain samples were obtained from four deceased patients who suffered an ICH including perihematomal tissue (PH) and the corresponding contralateral white (CW) and grey (CG) matter. Affymetrix GeneChip platform for analysis of over 47,000 transcripts was conducted. Microarray Analysis Suite 5.0 was used to process array images and the Ingenuity Pathway Analysis System was used to analyze biological mechanisms and functions of the genes. We identified 468 genes in the PH areas displaying a different expression pattern with a fold change between -3.74 and +5.16 when compared to the contralateral areas (291 overexpressed and 177 underexpressed). The top genes which appeared most significantly overexpressed in the PH areas codify for cytokines, chemokines, coagulation factors, cell growth and proliferation factors while the underexpressed codify for proteins involved in cell cycle or neurotrophins. Validation and replication studies at gene and protein level in brain samples confirmed microarray results.. The genomic responses identified in this study provide valuable information about potential biomarkers and target molecules altered in the perihematomal regions.

Topics: Aged; Aged, 80 and over; Brain Diseases; Cerebral Hemorrhage; Female; Gene Expression Profiling; Genome, Human; Hematoma; Humans; Interleukin-8; Male; Oligonucleotide Array Sequence Analysis; Rupture, Spontaneous; Validation Studies as Topic

Peri-intraventricular hemorrhage (P/IVH) is a common neonatal morbidity among premature infants. The aim of the study was to examine the association between placental and/or fetal inflammation and the onset of P/IVH in premature infants.. A prospective study included 125 infants with gestational age 23-29 weeks. Placentas were examined for the presence of chorioamnionitis and funisitis, cord blood was sampled for the measurement of cytokines (IL-6 and IL-8). Fetal inflammation was defined as levels of IL-6 higher than 7.6 pg/ml. P/IVH was defined as early if diagnosed within the 1st day after birth; thereafter P/IVH was defined as late.. Adjusted for the influence of gestational age, early-onset sepsis (OR 3.2, p = 0.045) and no or incomplete antenatal steroid course (OR 6.0, p = 0.001) significantly predicted early P/IVH. Funisitis (OR 1.6, p = 0.06) and fetal inflammation (OR 2.6, p = 0.06) were only partially associated with early hemorrhage. Contrary to that, respiratory distress syndrome (OR 3.4, p = 0.04), mechanical ventilation (OR 5.9, p = 0.008), low blood pressure (OR 3.5, p = 0.02), and vasopressors (OR 5.7, p = 0.002) were associated with late P/IVH. In multivariate analysis no or incomplete steroid course remained independent predictors for early and use of vasopressors for late P/IVH. The interaction of fetal inflammation and vaginal delivery with no or incomplete steroid course increased the risk of early P/IVH.. These results indicate different risk factors for early and late P/IVH. Neither funisitis nor fetal inflammation independently predicts the onset of P/IVH. However, the interaction of fetal inflammation and vaginal delivery with no or incomplete antenatal steroid course increase the risk of early but not also late P/IVH.

Topics: Cerebral Hemorrhage; Chorioamnionitis; Female; Fetal Blood; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Inflammation; Interleukin-6; Interleukin-8; Male; Multivariate Analysis; Pregnancy; Prospective Studies; Risk Factors

To investigate whether or not peri/intraventricular hemorrhages (PIVHs) occurring in the first 12 hours of life (early PIVHs) are related to respiratory distress syndrome (RDS)-associated inflammatory factors in contrast to PIVHs developing after 12 hours of life (late PIVHs).. Blood samples obtained at 0 to 12 hours, 48 to 72 hours, and 168 hours of life were evaluated for determination of the proinflammatory cytokines interleukin (IL)-8 and IL-6, tumor necrosis factor (TNF)-alpha, and malondialdehyde (MDA) as measures of lipid peroxidation. Simultaneously, cranial ultrasonography was performed in 114 neonates under 32 weeks gestational age.. Out of the total study group of 114 neonates, 67 (59%) had RDS. Early PIVH occurred in 16 neonates, 14 of whom (88%) had RDS. Late PIVHs occurred in 12 neonates. Neonates with RDS had higher IL-8 and IL-6 levels at 0 to 12 hours (P < .0001; < .0001) and at 48 to 72 hours (P < .001; < .01) than those without RDS. Neonates with early PIVH had higher IL-8 (P < .02), IL-6 (P < .02), and MDA (P < .01) levels at 0 to 12 hours than those with late PIVH or no PIVH. Those with early PIVH had higher IL-8 levels at 48 to 72 hours than those without PIVH (P < .02). Multiple linear regression revealed an association between RDS/early PIVH and IL-8, IL-6, and MDA levels.. An RDS-associated increase in proinflammatory cytokine and MDA levels was associated with early PIVHs, but not with late PIVHs, suggesting a different etiopathogenesis in early versus late PIVHs.

Topics: Age Factors; Cerebral Hemorrhage; Cytokines; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Inflammation; Interleukin-6; Interleukin-8; Linear Models; Lipid Peroxidation; Malondialdehyde; Oxidative Stress; Respiratory Distress Syndrome, Newborn; Tumor Necrosis Factor-alpha; Ultrasonography

To study the influence of beta-endorphin (beta end) on the function of immune system of patients with cerebral hemorrhage at different stages.. Radioimmunal analysis was applied to detect the serum beta-endorphin concentration in the peripheral blood of 28 patients with cerebral hemorrhage, aged 65.5 +/- 13, 28 age-matched patients with cerebral thrombosis, and 28 sex and age-matched normal controls. Mononuclear cells from peripheral blood of these 3 kinds of subjects were cultured and then beta end 10(-8) g/L, beta end 10(-11) g/L, beta end 10(-14) g/L, or beta end 10(-11) g/L + naloxone 10(-5) g/L were added into the media respectively and the MNCs were cultured for more 24 hours (beta end 10(-8) g/L group, beta end 10(-11) g/L group, beta end 10(-14) g/L group, and beta end 10(-11) g/L + Nal group). Another MNCs were cultured without addition of beta end (beta end 0 g/L group). Then the MNCs were collected. RT-PCR was used to detect the expressions of interleukin (IL)-1beta, IL-2, IL-8 and iNOS mRNA in the MNCs.. The serum beta-end level of the patients with cerebral hemorrhage at the acute stage was 129 +/- 82 ng/L, significantly lower than that of the normal controls (321 +/- 62 ng/L, P<0.01) and that of the patients with cerebral thrombosis (264 +/- 163 ng/L, P<0.05), but not significantly different from that of the patients with cerebral hemorrhage in the convalescent stage (160 +/- 72 ng/L, P>0.05). The expression of IL-1beta and the expression of IL-2 of the patients with cerebral hemorrhage at the acute stage were significantly lower than those of the patients with cerebral thrombosis and the controls (all P<0.01). The expression of IL-1beta of the patients with cerebral hemorrhage at the convalescent stage were higher than that in the acute stage, however, the difference was not significant (P>0.05). The expression of IL-2 of the patients with cerebral hemorrhage at the convalescent stage was higher than that at the acute stage (P<0.01). The expression of IL-8 and the expression of iNOS of the patients with cerebral hemorrhage at the acute stage were significantly higher than those of the patients of cerebral thrombosis and the controls (both P<0.01). The expression of IL-8 and the expression of iNOS of the patients with cerebral hemorrhage at the convalescent stage were significantly lower than those in the acute stage (both P<0.01). The expressions of IL-1beta, IL-2, IL-8, and iNOS mRNA in the peripheral blood MNCs in vitro in the beta end 10(-8) g/L group and beta end 10(-11) g/L group were significantly higher than those of the beta end 0 g/L group, beta end 10(-11) g/L group, and beta-end 10(-11) g/L + Nal 10(-5)g/L group. The expressions of IL-1beta, IL-2, IL-8, and iNOS mRNA in the peripheral blood MNCs in the beta-end 10(-11) g/L +Nal 10(-5) g/L group were higher than those of the beta end 0 g/L group, however, not significantly.. The endogenous beta-endorphin level of cerebral hemorrhage patients is low. The immune system function is up-regulated at the acute stage and then down-regulated. Thereafter the immune system function is invariably low. Exogenous beta-endorphin enhances the IL-1 beta, IL-2, IL-8 and iNOS mRNA expression of peripheral blood MNCS. beta-endorphin receptor antagonist naloxone blocks the positive immunoregulation by beta-endorphin.

Topics: Aged; Aged, 80 and over; beta-Endorphin; Cerebral Hemorrhage; Female; Humans; Immune System; Interleukin-8; Male; Middle Aged; Naloxone; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; RNA, Messenger

Posthaemorrhagic ventricular dilatation (PHVD) is closely associated with white matter damage and neurological disability in the preterm infant. Proinflammatory cytokines have been implicated in the pathogenesis of white matter injury and subsequent cerebral palsy. The aim of this study was to determine the levels of proinflammatory cytokines in cerebrospinal fluid (CSF) from preterm infants with PHVD and to correlate the levels to white matter damage and neurodevelopmental outcome.. CSF samples were obtained from 24 preterm infants with expanding PHVD and 19 preterm infants with normal ultrasound. Tumour necrosis factor-alphaa (TNF-alpha ), interleukin-1beta (IL-1beta), interleukin-8 (IL-8) and interferon-gamma (IFN-gamma) in CSF were measured by enzyme-linked immunosorbent assay, and IL-6 was measured by bioassay.. The concentrations of TNF-alpha, IL-1beta, IL-6 and IL-8 were significantly elevated in CSF from infants with PHVD. TNF-alpha was detected in 43% of PHVD infants and 11% of controls (p = 0.04). IL-1beta was detected in 67% of PHVD infants and 0% of controls (p < 0.0001). The concentrations of IL-6 were 368 (145-460) pg ml(-1) in the PHVD group and 30 (25-41) pg ml(-1) in the control group (p < 0.0001), and those of IL-8 were 3000 (1620-3400) pg ml(-1) in the PHVD group and 35 (0-230) pg ml(-1) in the control group (p < 0.0001). Cytokine concentrations did not correlate with white matter lesions on ultrasound, shunt dependence or neurological outcome within the PHVD group.. There was an intense and prolonged inflammatory reaction in CSF from preterm infants with PHVD and a high risk for subsequent white matter injury and permanent neurological impairment.

Topics: Cerebral Hemorrhage; Cerebral Ventricles; Cytokines; Dilatation, Pathologic; Humans; Infant, Newborn; Infant, Premature; Interferon-gamma; Interleukin-1; Interleukin-6; Interleukin-8; Tumor Necrosis Factor-alpha; Ultrasonography

This article investigates nitric oxide (NO) metabolism following severe head injury (SHI). We wished to clarify the alterations of NO metabolism end products that is associated with SHI, and to delineate the role of inflammation in this process.. In a prospective study, we simultaneously measured the concentrations of NO metabolites and interleukin-8 (IL-8) in the ventricular cerebrospinal fluid (CSF) of 11 patients who had suffered SHI. The CSF concentrations of nitrite (NO(-)(2)) and nitrate (NO(-)(3)) combined, and of IL-8 were measured during the following four time periods post-trauma: 6 to 10, 20 to 28, 40 to 56, and 64 to 74 hours. Levels were measured using the corresponding kits.. Compared to the ventricular CSF control values, all of our SHI patients had significantly elevated CSF levels of NO(-)(2) plus NO(-)(3) (NO(-)(2) + NO(-)(3)) and IL-8 during all periods tested. CSF NO(-)(2) + NO(-)(3) and IL-8 concentrations reached their maximums simultaneously at 20 to 28 hours following trauma (Spearman's rank correlation = 0.609, p < 0.05), and NO(-)(2) + NO(-)(3) levels were significantly higher than those measured at 6 to 10, 40 to 56, and 64 to 74 hours. [Nitrite-nitrate concentrations: 6-10 hours: 19.22 +/- 6.75, 20-28 hours: 25 +/- 6.2 micromol/l, 40-56 hours: 19.82 +/- 4.47, and 64-74 hours: 19.72 +/- 4.61 micromol/l, (p < 0.05). IL-8 concentrations: 6-10 hours: 3,232 +/- 2,976.2, 20-28 hours: 3,458.45 +/- 3,048 pg/mL, 40-56 hours: 2,616.41 +/- 2,539.21, 64-74 hours: 1,388.88 +/- 1,216.7 pg/mL, (p < 0.001).]. This simultaneous surge in NO(-)(2) + NO(-)(3) and IL-8 in the initial 24 hours post-traumatic indicated that inflammation secondary to SHI increased the rate of NO metabolism, resulting in higher levels of metabolites in the CSF.. In patients with SHI, CSF concentrations of the dominant metabolites of NO are elevated in the first 3 days after trauma. A similar concurrent spike in the CSF level of IL-8, a marker of acute inflammatory response, can also be demonstrated. These data indicate that the predominant cause of the higher CSF NO(-)(2) + NO(-)(3) concentrations observed in SHI is most likely inflammation.

Topics: Adolescent; Adult; Cerebral Hemorrhage; Child; Child, Preschool; Encephalitis; Female; Head Injuries, Closed; Humans; Interleukin-8; Male; Middle Aged; Nitrates; Nitric Oxide; Nitrites; Prognosis; Prospective Studies

To evaluate whether cerebrospinal fluid concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, or IL-8 may be used as diagnostic markers for the differential diagnosis of aseptic vs. bacterial meningitis and/or ventriculitis in neurosurgical patients.. Prospective, observational study.. University teaching hospital.. A total of 112 cerebrospinal fluid samples from 14 asymptomatic patients with normal cerebrospinal fluid after neurosurgery, 27 asymptomatic and 19 symptomatic patients with postneurosurgical aseptic meningitis, 32 patients with postneurosurgical cerebrospinal fluid infection, and 20 with severe subarachnoid and/or cerebral hemorrhage.. Specific ELISA kits were used to analyze TNF-alpha, IL-1beta, IL-6, and IL-8 concentrations on cerebrospinal fluid samples. Elevations in cerebrospinal fluid concentrations of TNF-alpha, IL-1beta, IL-6, and IL-8 were induced by different diseases or neurosurgical procedures, but cerebrospinal fluid bacterial infection induced the highest concentrations. To discriminate between aseptic cerebrospinal fluid pleocytosis and cerebrospinal fluid infection with a specificity of 95%, cerebrospinal fluid leukocyte count >1700/mL, TNF-alpha >150 pg/mL, and IL-1beta >90 pg/mL showed sensitivities of 51%, 74%, and 90%, respectively. Sufficiently sensitive and specific cutoff points could not be found for cerebrospinal fluid IL-6 or IL-8.. Cerebrospinal fluid IL-1beta appears to be the best biochemical marker of cerebrospinal fluid infection in neurosurgical patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Cerebral Hemorrhage; Child; Child, Preschool; Cytokines; Diagnosis, Differential; Encephalitis; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Male; Meningitis, Aseptic; Meningitis, Bacterial; Middle Aged; Neurosurgical Procedures; Postoperative Complications; Prospective Studies; Tumor Necrosis Factor-alpha

To study the effects of a spin trap agent and a CD18 antibody administered after stroke induction on intracerebral hemorrhaging. The drugs can prevent leukocyte adhesion.. A rabbit embolic stroke model that produces intracerebral hemorrhage was used.. A time course study showed that hemorrhaging was grossly apparent in approximately 50% of the subjects at 5 hours and in 75% at 24 hours after embolization. MDL 101,002, a spin trap agent, administered IV 5 minutes after embolization, significantly decreased the volume of hemorrhage. It also improved the behavior score relative to vehicle-treated rabbits. The CD18 antibody tended to decrease hemorrhage volume.. The beneficial effect of MDL 101,002 may be caused by inhibition of free radical injury to brain tissue, thereby protecting brain microvessel integrity. Acute therapy for intracerebral hemorrhage may be feasible.

Topics: Animals; Antibodies, Monoclonal; Brain; Brain Edema; CD18 Antigens; Cerebral Hemorrhage; Cerebral Infarction; Disease Models, Animal; Extravasation of Diagnostic and Therapeutic Materials; Interleukin-8; Intracranial Embolism; Isoquinolines; Nitrogen Oxides; Rabbits; Spin Labels