interleukin-8 and Autism-Spectrum-Disorder

Autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are associated with immune dysregulation. We aimed to estimate the pro- and anti-inflammatory activity/balance in ASD and ADHD patients at a little-studied adolescent age with respect to sex. We evaluated 20 ASD patients (5 girls, average age: 12.4 ± 1.9 y), 20 ADHD patients (5 girls, average age: 13.4 ± 1.8 y), and 20 age- and gender-matched controls (average age: 13.2 ± 1.9 y). The evaluated parameters included (1) white blood cells (WBCs), neutrophils, monocytes, lymphocytes, platelets, platelet distribution width (PDW), mean platelet volume, and derived ratios, as well as (2) cytokines-interferon-gamma, interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10, tumor necrosis factor-alpha (TNF-α), and derived profiles and ratios. ASD adolescents showed higher levels of WBC, monocytes, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10, macrophages (M)1 profile, and anti-inflammatory profile than the controls, with ASD males showing higher monocytes, IL-6 and IL-10, anti-inflammatory profile, and a lower T-helper (Th)1/Th2+T-regulatory cell ratio than control males. The ADHD adolescents showed higher levels of PDW, IL-1β and IL-6, TNF-α, M1 profile, proinflammatory profile, and pro-/anti-inflammatory ratio than the controls, with ADHD females showing a higher TNF-α and pro-/anti-inflammatory ratio than the control females and ADHD males showing higher levels of IL-1β and IL-6, TNF-α, and M1 profile than the control males. Immune dysregulation appeared to be different for both neurodevelopmental disorders in adolescence.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Child; Female; Humans; Interleukin-10; Interleukin-2; Interleukin-4; Interleukin-6; Interleukin-8; Male; Tumor Necrosis Factor-alpha

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an unclear etiology and pathophysiology. Previous studies have indicated that the dysregulation of cytokines may be involved in the pathogenesis of ASD and that the levels of cytokines may serve as potential biomarkers of this disorder.. The current study employed a family triad-based case-control design to study the levels of plasma cytokines in families with ASD (n = 45 triads) and controls (n = 38 triads) with a Human Cytokine Twenty-Five-Plex Kit. The Social Responsiveness Scale (SRS) was used to measure social impairment of ASD children.. After controlling for the levels of parental cytokines, we identified that interferon-α (IFN-α), interleukin-7 (IL-7), IL-8, IFN-γ-inducible protein-10, and macrophage inflammatory protein-1β were associated with ASD, and IL-8 was the only cytokine also associated with the levels of both parental cytokines in the offspring-parents regression analysis and three subdomains of SRS (social awareness, cognition, and motivations) in the children with ASD. The receiver operating characteristic curve showed that the log-transformed IL-8 level discriminated children with autism from controls with an area under the curve of 0.858 (95% confidence interval: 0.777-0.939).. Our study suggests that IL-8 is a potential biomarker for ASD and may be involved in the pathogenesis of ASD.. The study suggests that IL-8 is a promising biomarker for ASD and may be involved in the pathogenesis of ASD. Only a very few studies have reported the parental cytokine levels. The significant strength of this article is that we applied the family triad-based approach to explore cytokine levels in families with autism and controls. There are no objective biomarkers, making the accurate diagnosis, prognostic prediction and effective treatment difficult, and our study provides promising results.

Topics: Area Under Curve; Autism Spectrum Disorder; Biomarkers; Case-Control Studies; Child; Child, Preschool; China; Cross-Sectional Studies; Family Health; Female; Humans; Interferon-alpha; Interferon-gamma; Interleukin-7; Interleukin-8; Male; Regression Analysis; Reproducibility of Results; Sensitivity and Specificity; Social Behavior Disorders

Vitamin D is essential for several physiological functions and biological processes. Increasing levels of maternal vitamin D are required throughout pregnancy as a unique source of vitamin D for the fetus, and consequently maternal vitamin D deficiency may result in several adverse outcomes in newborns. However, the genetic regulation of vitamin D in pregnancy and at birth is not yet well understood. We performed genome-wide association studies of maternal midgestational serum-derived and neonatal blood-spot-derived total 25-hydroxyvitamin D from a case-control study of autism spectrum disorder (ASD). We identified one fetal locus (rs4588) significantly associated with neonatal vitamin D levels in the

Topics: Adult; Autism Spectrum Disorder; Chemokine CXCL6; Duffy Blood-Group System; Female; Fetal Blood; Humans; Infant, Newborn; Interleukin-8; Polymorphism, Single Nucleotide; Pregnancy; Protein Kinase C; Receptors, Cell Surface; Vitamin D; Vitamin D-Binding Protein

Autism spectrum disorder (ASD) does not have a distinct pathogenesis or effective treatment. Increasing evidence supports the presence of immune dysfunction and inflammation in the brains of children with ASD. In this report, we present data that gene expression of the antiinflammatory cytokine IL-37, as well as of the proinflammatory cytokines IL-18 and TNF, is increased in the amygdala and dorsolateral prefrontal cortex of children with ASD as compared to non-ASD controls. Gene expression of IL-18R, which is a receptor for both IL-18 and IL-37, is also increased in the same brain areas of children with ASD. Interestingly, gene expression of the NTR3/sortilin receptor is reduced in the amygdala and dorsolateral prefrontal cortex. Pretreatment of cultured human microglia from normal adult brains with human recombinant IL-37 (1 to 100 ng/mL) inhibits neurotensin (NT)-stimulated secretion and gene expression of IL-1β and CXCL8. Another key finding is that NT, as well as the proinflammatory cytokines IL-1β and TNF increase IL-37 gene expression in cultured human microglia. The data presented here highlight the connection between inflammation and ASD, supporting the development of IL-37 as a potential therapeutic agent of ASD.

Topics: Adaptor Proteins, Vesicular Transport; Amygdala; Autism Spectrum Disorder; Cells, Cultured; Child; Humans; Interleukin-1; Interleukin-18; Interleukin-18 Receptor alpha Subunit; Interleukin-1beta; Interleukin-8; Microglia; Neurotensin; Prefrontal Cortex; Tumor Necrosis Factor-alpha

Among the 1 of 10 children who are born preterm annually in the United States, 6% are born before the third trimester. Among children who survive birth before the 28th week of gestation, the risks of autism spectrum disorder (ASD) and non-autistic social impairment are severalfold higher than in the general population. We examined the relationship between top quartile inflammation-related protein concentrations among children born extremely preterm and ASD or, separately, a high score on the Social Responsiveness Scale (SRS total score ≥65) among those who did not meet ASD criteria, using information only from the subset of children whose DAS-II verbal or non-verbal IQ was ≥70, who were assessed for ASD, and who had proteins measured in blood collected on ≥2 days (N = 763). ASD (N = 36) assessed at age 10 years is associated with recurrent top quartile concentrations of inflammation-related proteins during the first post-natal month (e.g., SAA odds ratio (OR); 95% confidence interval (CI): 2.5; 1.2-5.3) and IL-6 (OR; 95% CI: 2.6; 1.03-6.4)). Top quartile concentrations of neurotrophic proteins appear to moderate the increased risk of ASD associated with repeated top quartile concentrations of inflammation-related proteins. High (top quartile) concentrations of SAA are associated with elevated risk of ASD (2.8; 1.2-6.7) when Ang-1 concentrations are below the top quartile, but not when Ang-1 concentrations are high (1.3; 0.3-5.8). Similarly, high concentrations of TNF-α are associated with heightened risk of SRS-defined social impairment (N = 130) (2.0; 1.1-3.8) when ANG-1 concentrations are not high, but not when ANG-1 concentrations are elevated (0.5; 0.1-4.2).

Topics: Autism Spectrum Disorder; Child; Female; Humans; Infant, Extremely Premature; Infant, Newborn; Inflammation; Interleukin-6; Interleukin-8; Logistic Models; Male; Prospective Studies; Psychiatric Status Rating Scales; Risk Assessment; Serum Amyloid A Protein; Tumor Necrosis Factor-alpha; United States

Autism spectrum disorder (ASD) affects approximately 1 in 68 children in the USA. An ASD blood biomarker may enable early diagnosis and/or identification of new therapeutic targets. Serum samples from ASD and typically developing (TD) boys (n = 30/group) were screened for differences in 110 proteins using a multiplex immunoassay.. Eleven proteins were found that together could confirm ASD with modest accuracy using multiple training and test sets. Two of the 11 proteins identified here were further tested using a different detection platform and with a larger sample of ASD and TD boys. The two proteins, thyroid-stimulating hormone (TSH) and interleukin-8 (IL-8), have been previously identified as putative biomarkers for ASD. TSH levels were significantly lower in ASD boys, whereas IL-8 levels were significantly elevated. The diagnostic accuracy for ASD based upon TSH or IL-8 levels alone varied from 74 to 76%, but using both proteins together, the diagnostic accuracy increased to 82%. In addition, TSH levels were negatively correlated with the Autism Diagnostic Observation Schedule subdomain scores.. These data suggest that a panel of proteins may be useful as a putative blood biomarker for ASD.

Topics: Autism Spectrum Disorder; Child; Child, Preschool; Humans; Interleukin-8; Luminescent Measurements; Male; Regression Analysis; ROC Curve; Severity of Illness Index; Thyrotropin

Autism spectrum disorders (ASD) are complex conditions whose pathogenesis may be attributed to gene-environment interactions. There are no definitive mechanisms explaining how environmental triggers can lead to ASD although the involvement of inflammation and immunity has been suggested. Inappropriate antigen trafficking through an impaired intestinal barrier, followed by passage of these antigens or immune-activated complexes through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to these disorders. Our goal was to investigate whether an altered BBB and gut permeability is part of the pathophysiology of ASD.. Claudin (. In the ASD brain, there is an altered expression of genes associated with BBB integrity coupled with increased neuroinflammation and possibly impaired gut barrier integrity. While these findings seem to be specific for ASD, the possibility of more distinct SCZ subgroups should be explored with additional studies.

Topics: Adolescent; Adult; Autism Spectrum Disorder; Biopsy; Blood-Brain Barrier; Calcium-Binding Proteins; Case-Control Studies; Cerebellum; Cerebral Cortex; Child; Child, Preschool; Claudin-3; Claudin-5; Claudins; DNA-Binding Proteins; Duodenum; Female; Gene Expression; Humans; Interleukin-1beta; Interleukin-8; Male; MARVEL Domain Containing 2 Protein; Matrix Metalloproteinase 9; Microfilament Proteins; Middle Aged; Permeability; Schizophrenia; Tight Junctions