interleukin-8 and Cerebral-Palsy

An exacerbated systemic inflammatory response has been associated with the occurrence of central nervous system injuries that may determine, in long term, motor, sensorial and cognitive disabilities. Persistence of this exacerbated inflammatory response seems to be involved in the pathophysiology of cerebral palsy (CP).. A systematic search was conducted in Bireme, Embase, PubMed and Scopus including studies that were published until August 2019. The key words used were "cerebral palsy", "brain injury", "inflammation", "oxidative stress", "cytokines", "chemokines", "neuropsychomotor development", "neurodevelopment outcomes" and "child". The quality of the eligible studies was determined according to the criteria suggested by the Newcastle-Ottawa Scale (NOS).. Fourteen eligible studies aimed to investigate the association between peripheral inflammatory molecules and neurodevelopment in infants. The studies differed regarding CP-related risk factors and its classification. Inflammatory proteins were measured in blood, plasma, serum, cerebrospinal fluid or urine. In ten studies, higher circulating levels of cytokines, including IL-1β, IL-6, TNF and CXCL8/IL-8, were associated with abnormal neurological findings.. The investigation of the potential association between inflammatory molecules and neurological development in children with CP requires further original studies in order to clarify the influence of prenatal and perinatal inflammation on neurological outcomes.

Topics: Biomarkers; Cerebral Palsy; Cytokines; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Oxidative Stress; Tumor Necrosis Factor-alpha

To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay (NDD).. Nested case-control analysis within a clinical trial of antenatal magnesium sulfate (MgSO4) before anticipated preterm birth (PTB) for prevention of CP, with evaluation of surviving children at the age of 2. NDD was defined as a Bayley psychomotor developmental index (PDI) and/or mental developmental index (MDI) < 70. Controls, defined as surviving children without CP and with Bayley PDI and MDI ≥ 85, were matched by race and gestational age. Cord serum was analyzed for interleukin-8 (IL-8) interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α) levels. Elevated cytokine levels were defined as ≥ 75th percentile in placebo-exposed controls. Analyses compared case/control cytokine levels, adjusting for MgSO4 exposure, gestational age, race/ethnicity, and sociodemographic differences.. Logistic regression analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1β were more common in cord blood serum from infants with subsequent low MDI as compared with controls. After adjusting for additional confounders, the significant differences were no longer evident. Cytokine levels (IL-8, IL-1β, and TNF-α) were not elevated with CP or low PDI.. Cord serum IL-8, IL-1β, and TNF-α levels in preterm infants are not associated with subsequent CP or NDD.

Topics: Adult; Case-Control Studies; Cerebral Palsy; Child Development; Child, Preschool; Cytokines; Developmental Disabilities; Female; Fetal Blood; Humans; Infant; Infant, Newborn; Infant, Premature; Interleukin-1beta; Interleukin-8; Logistic Models; Magnesium Sulfate; Pregnancy; Premature Birth; Prognosis; Tocolytic Agents; Tumor Necrosis Factor-alpha; Young Adult

To evaluate the relation among gingival inflammation, salivary osmolality, levels of IL-1β, IL-6, IL-8, TNF-α, and s-IgA concentrations in children with spastic CP with or without cervical motor control in a cross-sectional study.. Unstimulated whole saliva and the gingival index were collected in 37 and 34 CP children with and without cervical motor control, respectively. The data were dichotomized as follows: (=0) absence of gingival inflammation and (≥0.1) presence of gingival inflammation.. The group without cervical control presented statistically higher mean values of salivary osmolality, s-IgA, and cytokines. In addition, statistically positive correlation between the gingival index and salivary cytokines was observed in the group with cervical control. Salivary osmolality, salivary cytokines, and s-IgA from both groups presented a significant positive correlation. Significant differences (P = 0.00336) in the values of salivary osmolality were observed between the CP individuals with (93.9 ± 32.7) and without gingival inflammation (74.4 ± 16.6). ROC analysis was performed, and values of salivary osmolality >80 indicated a sensitivity of 0.54 and a specificity of 0.79.. Children without cervical motor control presented a more pronounced oral inflammatory status that was characterized by higher levels of cytokines.

Topics: Adolescent; Biomarkers; Brazil; Cerebral Palsy; Child; Cross-Sectional Studies; Cytokines; Female; Gingivitis; Humans; Immunoglobulin A; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Osmolar Concentration; Periodontal Index; Rehabilitation; Saliva; Tumor Necrosis Factor-alpha

The objective of this study was to examine whether selected genetic polymorphisms in the infant are associated with later-diagnosed cerebral palsy.. A population-based case-control study was conducted of 28 single-nucleotide polymorphisms measured in newborn screening blood spots. A total of 413 children with later-diagnosed cerebral palsy were born to white women in South Australia in 1986-1999, and there were 856 control children. Distributions of genotypic frequencies were examined in total cerebral palsy, in gestational age groups, and by types of cerebral palsy and gender. Genotyping was performed by using a TaqMan assay.. For inducible nitric-oxide synthase, possession of the T allele was more common in all children with cerebral palsy and for heterozygotes who were born at term. For lymphotoxin alpha, homozygous variant status was associated with risk for cerebral palsy and with spastic hemiplegic or quadriplegic cerebral palsy. Among term infants, heterozygosity for the endothelial protein C receptor single-nucleotide polymorphism was more frequent in children with cerebral palsy. In preterm infants, the variant A allele of interleukin 8 and heterozygosity for the beta-2 adrenergic receptor were associated with cerebral palsy risk. Interleukin 8 heterozygote status was associated with spastic diplegia. Variants of several genes were associated with cerebral palsy in girls but not in boys.. Two of the 28 single-nucleotide polymorphisms examined were associated with all types of spastic cerebral palsy in both gestational age groups and others with cerebral palsy in gestational age or cerebral palsy subgroups. Some of these associations support previous findings. There may be a genetic contribution to cerebral palsy risk, and additional investigation is warranted of genes and gene-environment interactions in cerebral palsy.

Topics: 5-Lipoxygenase-Activating Proteins; Antigens, CD; Carrier Proteins; Case-Control Studies; Cerebral Palsy; Endothelial Protein C Receptor; Female; Genetic Predisposition to Disease; Genotype; Humans; Infant, Newborn; Infant, Premature; Interleukin-8; Male; Membrane Proteins; Neonatal Screening; Nitric Oxide Synthase Type II; Plasminogen Activator Inhibitor 1; Polymorphism, Single Nucleotide; Protein C; Receptors, Adrenergic, beta-2; Receptors, Cell Surface; Risk Assessment; Seroepidemiologic Studies; South Australia

Preterm birth carries a risk for impaired developmental outcome. We have previously described an association between increased levels of proinflammatory cytokines during the first 72 postnatal hours and cerebral damage as detected by ultrasound in a cohort of 74 very preterm infants. Sixty-seven of 71 surviving children with a mean gestational age of 27.1 (2.0) wk were examined at 2 y corrected age with a standardized neurologic examination and with Bayley Scales of Infant Development. We hypothesized that proinflammatory cytokine concentrations at or shortly after birth would be associated with an adverse developmental outcome. Increased concentrations of TNF-alpha in cord blood odds ratio (95% confidence interval) 3.3 (1.1-10.2), p = 0.013 and at 6 h 7.8 (0.9-71.8), p = 0.015 and of IL-6 in cord blood 1.7 (1.0-2.9), p = 0.048 were associated with psychomotor developmental index <85. Increased concentrations of TNF-alpha in cord blood odds ratio (95% confidence interval) 3.6 (1.002-12.8), p = 0.044 and of IL-8 in cord blood 3.5 (1.2-10.6), p = 0.023 were associated with cerebral palsy. Associations of TNF-alpha and IL-8 in cord blood with the respective outcome measures remained significant after adjustment for other clinical variables. Proinflammation at birth is associated with impaired functional outcome at 2 y of corrected age in children with very preterm birth.

Topics: Cerebral Palsy; Child Development; Child, Preschool; Cohort Studies; Follow-Up Studies; Humans; Infant, Newborn; Infant, Premature; Inflammation; Interleukin-6; Interleukin-8; Outcome Assessment, Health Care; Psychomotor Disorders; Risk Factors; Single-Blind Method; Tumor Necrosis Factor-alpha

Many studies have shown that certain cytokines in amniotic fluids are correlated to premature labor and neonatal brain insults.. We investigated whether different fetal phagocyte and vascular mediators including IL-8, myeloperoxidase (MPO), PGE(2) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were correlated to prematurity and cerebral palsy (CP) of premature infants.. Umbilical cord blood samples from 96 preterm babies from 2250 cord blood collections were studied.. The enzyme-linked immunoassay (ELISA) technique was used to determine concentrations of cord blood IL-8, MPO, PGE(2) and sVCAM-1.. Preterm babies with gestational age (GA) < or =32 weeks had significant higher cord blood IL-8, MPO and PGE(2) levels than full-term babies. These mediators, however, were not correlated to gestational age, suggesting that increases of these mediators are more related to preterm delivery but not fetal maturation. Further analysis showed that IL-8, a mediator mainly from monocytes, but not MPO, another mediator mostly from granulocytes, was correlated to cerebral palsy.. Taken together, these results suggest that both premature monocytes and granulocytes activation are involved in preterm delivery, but maybe only monocytes activation is correlated to premature infants' cerebral palsy. Selective manipulation of monocytes activation may be useful to prevent premature-related cerebral palsy.

Topics: Cerebral Palsy; Cytokines; Dinoprostone; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Interleukin-8; Male; Peroxidase; Pregnancy; Vascular Cell Adhesion Molecule-1

The aim of this study was to determine whether fetal exposure to intra-amniotic inflammation and a systemic fetal inflammatory response (funisitis) are associated with the development of cerebral palsy at the age of 3 years.. This cohort study included 123 preterm singleton newborns (gestational age at birth, /=3 years. The presence of intra-amniotic inflammation was determined by elevated amniotic fluid concentrations of proinflammatory cytokines such as interleukins 6 and 8 and by amniotic fluid white blood cell count. Cytokine concentrations were measured with sensitive and specific immunoassays. Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton jelly. Cerebral palsy was diagnosed by neurologic examination at the age of 3 years.. Newborns with subsequent development of cerebral palsy had a higher rate of funisitis and were born to mothers with higher median concentrations of interleukins 6 and 8 and higher white blood cell counts in the amniotic fluid compared with newborns without subsequent development of cerebral palsy (funisitis: 75% [9/12] vs 23% [24/105]; interleukin 6: median, 18.9 ng/mL; range, 0. 02-92.5 ng/mL; vs median, 1.0 ng/mL; range, 0.01-115.2 ng/mL; interleukin 8: median, 13.0 ng/mL; range, 0.1-294.5 ng/mL; vs median, 1.2 ng/mL; range, 0.05-285.0 ng/mL; white blood cell count: median, 198 cells/mm(3); range, 0->1000 cells/mm(3); vs median, 3 cells/mm(3); range, 0-19,764 cells/mm(3); P <.01 for each). After adjustment for the gestational age at birth, the presence of funisitis and elevated concentrations of interleukins 6 and 8 in amniotic fluid significantly increased the odds of development of cerebral palsy (funisitis: odds ratio, 5.5; 95% confidence interval, 1.2-24.5; interleukin 6: odds ratio, 6.4; 95% confidence interval, 1. 3-33.0; interleukin 8: odds ratio, 5.9; 95% confidence interval, 1. 1-30.7; P <.05 for each).. Antenatal exposure to intra-amniotic inflammation and evidence of a systemic fetal inflammatory response (funisitis) are strong and independent risk factors for the subsequent development of cerebral palsy at the age of 3 years.

Topics: Amniotic Fluid; Cerebral Palsy; Child, Preschool; Chorioamnionitis; Female; Humans; Interleukin-6; Interleukin-8; Leukocyte Count; Multivariate Analysis; Predictive Value of Tests; Pregnancy; Prenatal Exposure Delayed Effects