Interleukin-1β, Interleukin-18, and Interferon-γ Expression in the Cerebrospinal Fluid of Premature Infants with Posthemorrhagic Hydrocephalus—Markers of White Matter Damage? (original) (raw)
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American Journal of Obstetrics and Gynecology, 1997
OBJECTIVE: Ultrasonographically detectable neonatal brain white matter lesions are the most important identifiable risk factor for cerebral palsy. Inflammatory cytokines released during the course of intrauterine infections have been implicated in the genesis of brain white matter lesions and subsequent cerebral palsy. This study was undertaken to determine whether fetuses who subsequently were diagnosed to have periventricular brain white matter lesions could be identified by determining the concentrations of inflammatory cytokines in the amniotic fluid. STUDY DESIGN: Women with complicated preterm gestations underwent amniocentesis for clinical indications. Amniotic fluid concentrations of tumor necrosis factor-s, interleukin-l~B, interleukin-6, and the natural interleukin-1 receptor antagonist were determined by immunoassay. Periventricular white matter lesions of the neonate were diagnosed by neurosonography. Univariate and multivariate analyses were conducted. RESULTS: Ninety-four women and their neonates were included in the study; white matter lesions were diagnosed in 24% (23/94) of the newborns. The mothers of newborns with brain white matter lesions had higher median concentrations of tumor necrosis factor-c~, interleukin-l~, and interleukin-6 (but not interleukin-1 receptor antagonist) in amniotic fluid than did those who were delivered of newborns without white matter lesions (p < 0.01 for each). Acute histologic chorioaminionitis was more common in the placentas of neonate with white matter lesions than in those without these lesions (82% [18/22] vs 42% [30/71], p < 0.005). Neonates with white matter lesions were delivered at a lower mean gestational age and birth weight and had a higher rate of significant complications (including respiratory distress syndrome, intraventricular hemorrhage, and infectionrelated complications) than did those without white matter lesions. The differences in median interleukin-l~8 and interleukin-6 levels between these two groups remained significant after adjustment for gestational age and birth weight (interleukin-6: odds ratio 5.7, 95% confidence interval 1.3 to 24.4; interleukin-1 [3: odds ratio 4.4, 95% confidence interval 1.1 to 17.0). Of the 94 newborns included in this study, 11 died before age 6 months and eight had cerebral palsy; all eight had white matter lesions and elevated cytokine levels in amniotic fluid. Histologic chodoamnionitis was more common in the placentas of neonates with cerebral palsy than in those without cerebral palsy (86% [6/7] vs 44% [33/75], p < 0.05). CONCLUSIONS: Infants at risk for development of brain white matter lesions can be identified by the concentrations of interleukin-6 and interleukin-1 [3 in amniotic fluid. Our findings support the hypothesis that inflammatory cytokines released during the course of intrauterine infection play a role in the genesis of brain white matter lesions. (Am J Clinical and epidemiologic evidence indicates that brain white matter lesions detected with neurosonography during the neonatal period are the most accurate predictor of cerebral palsy in low-birth-weight infants? These lesions include echodensities and echolucencies From the
Fluids and barriers of the CNS, 2017
Neuroinflammation has been implicated in the pathophysiology of post-hemorrhagic hydrocephalus (PHH) of prematurity, but no comprehensive analysis of signaling molecules has been performed using human cerebrospinal fluid (CSF). Lumbar CSF levels of key cytokines (IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, TNF-α, TGF-β1, IFN-γ) and chemokines (XCL-1, CCL-2, CCL-3, CCL-19, CXCL-10, CXCL-11, CXCL-12) were measured using conventional and multiplexed Enzyme-linked Immunosorbent Assays and compared between preterm infants with PHH and those with no known neurological injury. The relationships between individual biomarker levels and specific CSF cell counts were examined. Total protein (TP) CSF levels were elevated in the PHH subjects compared to controls. CSF levels of IL-1α, IL-4, IL-6, IL-12, TNF-α, CCL-3, CCL-19, and CXCL-10 were significantly increased in PHH whereas XCL-1 was significantly decreased in PHH. When normalizing by TP, IL-1α, IL-1β, IL-10, IL-12, CCL-3, and CCL-19 leve...
Central nervous system immune response in postinfectious hydrocephalus
2020
ABSTRACTInflammation following neonatal infection is a dominant cause of childhood hydrocephalus in the developing world. Understanding this complex inflammatory response is critical for the development of preventive therapies. In 100 African hydrocephalic infants ≤3 months of age, with and without a history of infection, we elucidated the biological pathways that account for this inflammatory response. We integrated proteomics and RNA sequencing in cerebrospinal fluid, identifying gene pathways involving neutrophil, interleukin (4, 12, and 13) and interferon activity associated with this condition. These findings are required to develop strategies to reduce the risk of hydrocephalus during treatment of infection.
Folia neuropathologica, 2017
Cytokines are widely known mediators of inflammation accompanying many neurodegenerative disorders including normal pressure hydrocephalus (NPH). NPH is caused by impaired cerebrospinal fluid (CSF) absorption and treated by surgical shunt insertion. The early diagnosis of NPH is difficult because of various manifestations of the disease. One of the most promising research directions is biochemical CSF analysis. The aim of this study was to determine the CSF levels of cytokines. The levels of various cytokines (IL-6, IL-8, IL-12, IL-10 and TNF-α) were measured in patients with idiopathic active normal pressure hydrocephalus, arrested hydrocephalus and hydrocephalus with brain atrophy compared to controls. Our study showed that the concentrations of IL-6 and IL-8 were significantly elevated in the group with idiopathic active hydrocephalus compared to control patients. Moreover, we observed that the levels of IL-6 and IL-8 in the group with idiopathic active hydrocephalus were significantly higher compared to patients with arrested hydrocephalus and hydrocephalus with brain atrophy.
Clinical Chorioamnionitis, Elevated Cytokines, and Brain Injury in Term Infants
PEDIATRICS, 2002
To determine the initial inflammatory cytokine response in term infants born to mothers with clinical chorioamnionitis and to assess whether the cytokine response is associated with birth depression, abnormal neurologic examination, and hypoxic-ischemic encephalopathy (HIE). Infants who were exposed to chorioamnionitis and admitted to the neonatal intensive care unit (n = 61) were studied prospectively. Cytokine concentrations were measured from umbilical cord blood and at 6 and 30 hours after birth. Control values (n = 50) were determined from cord blood of healthy term infants. Enzyme-linked immunosorbent assays were performed for interleukin (IL)-1beta; IL-6; IL-8; regulated on activation, normal T-cell expressed and secreted (RANTES); macrophage inflammatory protein-1alpha; and tumor necrosis factor-alpha. Serial blinded neurologic examinations using a modified Dubowitz score were performed simultaneously at 6 and 30 hours. Cord IL-6 (1071 +/- 1517 vs 65 +/- 46 pg/mL), IL-8 (2580 +/- 9834 vs 66 +/- 57 pg/mL), and RANTES (95 917 +/- 16 518 vs 54 000 +/- 14 306 pg/mL) concentrations only were higher in infants with chorioamnionitis versus control infants. IL-6 increased at 6 hours to 1451 +/- 214 pg/mL, followed by a 5-fold decline at 30 hours in contrast to progressive decreases over time in IL-8 and RANTES. There was no relationship between cytokines and birth depression. Modified Dubowitz score correlated with IL-6 at 6 hours (r = 0.5). Infants with HIE/seizures (n = 5) had significantly higher cytokine concentrations at 6 hours versus infants without either (n = 56): IL-6 (3130 vs 1219 pg/mL), IL-8 (5433 vs 780 pg/mL), and RANTES (97 396 vs 46 914 pg/mL). There was a significant association between abnormalities in the neurologic examination and cytokine concentrations, with the highest cytokines concentrations observed in infants who developed HIE/seizures.
Archives of Disease in Childhood-fetal and Neonatal Edition, 1998
Aim-To determine the predictive value of plasma and cerebrospinal fluid (CSF) tumour necrosis factor-(TNF-) and interleukin-1 (IL-1 ) concentrations on the outcome of hypoxic-ischaemic encephalopathy (HIE) in full term infants. Methods-Thirty term infants with HIE were included in the study. HIE was classified according to the criteria of Sarnat and Sarnat. Blood and CSF were obtained within the first 24 hours of life and stored until assay. Five infants died soon after hypoxic insult. Neurological examinations and Denver Developmental Screening Test (DDST) were performed at 12 months in the survivors. Results-At the age of 12 months neurological examination and DDST showed that 11 infants were normal; 14 had abnormal neurological findings and/or an abnormal DDST result. Eleven normal infants were classified as group 1 and 19 infants (14 with abnormal neurological findings and/or an abnormal DDST and five who died) as group 2. CSF IL-1 and TNF-concentrations in group 2 were significantly higher than those in group 1. Plasma IL-1 and TNF-concentrations were not significantly diVerent between the two groups. IL-1 , but not TNF-concentrations, in group 2 were even higher than those in group 1, although nonsurvivors were excluded from group 2. When the patients were evaluated according to the stages of Sarnat, the diVerence in the three groups was again significant. Patients whose CSF samples were taken within 6 hours of the hypoxic insult had higher IL-1 and TNF-concentrations than the patients whose samples were taken after 6 hours. Conclusions-Both cytokines probably contribute to the damage sustained by the central nervous system after hypoxic insult. IL-1 seems to be a better predictor of HIE than TNF-.
Archives of Disease in Childhood-fetal and Neonatal Edition, 1998
Aim-To determine the predictive value of plasma and cerebrospinal fluid (CSF) tumour necrosis factor-(TNF-) and interleukin-1 (IL-1 ) concentrations on the outcome of hypoxic-ischaemic encephalopathy (HIE) in full term infants. Methods-Thirty term infants with HIE were included in the study. HIE was classified according to the criteria of Sarnat and Sarnat. Blood and CSF were obtained within the first 24 hours of life and stored until assay. Five infants died soon after hypoxic insult. Neurological examinations and Denver Developmental Screening Test (DDST) were performed at 12 months in the survivors. Results-At the age of 12 months neurological examination and DDST showed that 11 infants were normal; 14 had abnormal neurological findings and/or an abnormal DDST result. Eleven normal infants were classified as group 1 and 19 infants (14 with abnormal neurological findings and/or an abnormal DDST and five who died) as group 2. CSF IL-1 and TNF-concentrations in group 2 were significantly higher than those in group 1. Plasma IL-1 and TNF-concentrations were not significantly diVerent between the two groups. IL-1 , but not TNF-concentrations, in group 2 were even higher than those in group 1, although nonsurvivors were excluded from group 2. When the patients were evaluated according to the stages of Sarnat, the diVerence in the three groups was again significant. Patients whose CSF samples were taken within 6 hours of the hypoxic insult had higher IL-1 and TNF-concentrations than the patients whose samples were taken after 6 hours. Conclusions-Both cytokines probably contribute to the damage sustained by the central nervous system after hypoxic insult. IL-1 seems to be a better predictor of HIE than TNF-.