Preliminary evidence of the in vitro effects of BDE-47 on innate immune responses in children with autism spectrum disorders

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Abstract

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders that manifest in childhood. Immune dysregulation and autoimmune reactivity may contribute to the etiology of ASD and are likely the result of both genetic and environmental susceptibilities. A common environmental contaminant, 2,2′,4,4′-tetrabrominated biphenyl (BDE-47), was tested for differential effects on the immune response of peripheral blood mononuclear cells (PBMC) isolated from children with ASD (n = 19) and age-matched typically developing controls (TD, n = 18). PBMC were exposed in vitro to either 100 nM or 500 nM BDE-47, before challenge with bacterial lipopolysaccharide (LPS), an innate immune activator, with resultant cytokine production measured using the Luminex™ multiplex platform. The cytokine responses of LPS stimulated PBMC from ASD and TD subjects diverged in the presence of 100 nM BDE. For example, cells cultured from the TD group demonstrated significantly decreased levels of the cytokines IL-12p40, GM-CSF, IL-6, TNFα, and the chemokines MIP-1α and MIP-1β following LPS stimulation of PBMC pretreated with 100 nM BDE-47 compared with samples treated with vehicle control (p < 0.05). In contrast, cells cultured from subjects with ASD demonstrated an increased IL-1β response to LPS (p = 0.033) when pretreated with 100 nM BDE-47 compared with vehicle control. Preincubation with 500 nM BDE-47 significantly increased the stimulated release of the inflammatory chemokine IL-8 (p < 0.04) in cells cultured from subjects with ASD but not in cells from TD controls. These data suggest that in vitro exposure of PBMC to BDE-47 affects cell cytokine production in a pediatric population. Moreover, PBMC from the ASD subjects were differentially affected when compared with the TD controls suggesting a biological basis for altered sensitivity to BDE-47 in the ASD population.

Original languageEnglish (US)
Pages (from-to)130-135
Number of pages6
JournalJournal of Neuroimmunology
Volume208
Issue number1-2
DOIs
StatePublished - Mar 31 2009

Fingerprint

Innate Immunity
Blood Cells
Lipopolysaccharides
Cytokines
Cultured Cells
Chemokines
Interleukin-12 Subunit p40
2,2',4,4'-tetrabromodiphenyl ether
In Vitro Techniques
Autism Spectrum Disorder
Genetic Predisposition to Disease
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-8
Interleukin-1
Population
Interleukin-6
Pediatrics

Keywords

  • ASD
  • Autism
  • BDE-47
  • Innate immunity
  • LPS
  • Monocyte

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

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title = "Preliminary evidence of the in vitro effects of BDE-47 on innate immune responses in children with autism spectrum disorders",
abstract = "Autism spectrum disorders (ASD) are complex neurodevelopmental disorders that manifest in childhood. Immune dysregulation and autoimmune reactivity may contribute to the etiology of ASD and are likely the result of both genetic and environmental susceptibilities. A common environmental contaminant, 2,2′,4,4′-tetrabrominated biphenyl (BDE-47), was tested for differential effects on the immune response of peripheral blood mononuclear cells (PBMC) isolated from children with ASD (n = 19) and age-matched typically developing controls (TD, n = 18). PBMC were exposed in vitro to either 100 nM or 500 nM BDE-47, before challenge with bacterial lipopolysaccharide (LPS), an innate immune activator, with resultant cytokine production measured using the Luminex™ multiplex platform. The cytokine responses of LPS stimulated PBMC from ASD and TD subjects diverged in the presence of 100 nM BDE. For example, cells cultured from the TD group demonstrated significantly decreased levels of the cytokines IL-12p40, GM-CSF, IL-6, TNFα, and the chemokines MIP-1α and MIP-1β following LPS stimulation of PBMC pretreated with 100 nM BDE-47 compared with samples treated with vehicle control (p < 0.05). In contrast, cells cultured from subjects with ASD demonstrated an increased IL-1β response to LPS (p = 0.033) when pretreated with 100 nM BDE-47 compared with vehicle control. Preincubation with 500 nM BDE-47 significantly increased the stimulated release of the inflammatory chemokine IL-8 (p < 0.04) in cells cultured from subjects with ASD but not in cells from TD controls. These data suggest that in vitro exposure of PBMC to BDE-47 affects cell cytokine production in a pediatric population. Moreover, PBMC from the ASD subjects were differentially affected when compared with the TD controls suggesting a biological basis for altered sensitivity to BDE-47 in the ASD population.",
keywords = "ASD, Autism, BDE-47, Innate immunity, LPS, Monocyte",
author = "Paul Ashwood and Joseph Schauer and Pessah, {Isaac N} and {Van de Water}, {Judith A}",
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AU - Ashwood, Paul

AU - Schauer, Joseph

AU - Pessah, Isaac N

AU - Van de Water, Judith A

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N2 - Autism spectrum disorders (ASD) are complex neurodevelopmental disorders that manifest in childhood. Immune dysregulation and autoimmune reactivity may contribute to the etiology of ASD and are likely the result of both genetic and environmental susceptibilities. A common environmental contaminant, 2,2′,4,4′-tetrabrominated biphenyl (BDE-47), was tested for differential effects on the immune response of peripheral blood mononuclear cells (PBMC) isolated from children with ASD (n = 19) and age-matched typically developing controls (TD, n = 18). PBMC were exposed in vitro to either 100 nM or 500 nM BDE-47, before challenge with bacterial lipopolysaccharide (LPS), an innate immune activator, with resultant cytokine production measured using the Luminex™ multiplex platform. The cytokine responses of LPS stimulated PBMC from ASD and TD subjects diverged in the presence of 100 nM BDE. For example, cells cultured from the TD group demonstrated significantly decreased levels of the cytokines IL-12p40, GM-CSF, IL-6, TNFα, and the chemokines MIP-1α and MIP-1β following LPS stimulation of PBMC pretreated with 100 nM BDE-47 compared with samples treated with vehicle control (p < 0.05). In contrast, cells cultured from subjects with ASD demonstrated an increased IL-1β response to LPS (p = 0.033) when pretreated with 100 nM BDE-47 compared with vehicle control. Preincubation with 500 nM BDE-47 significantly increased the stimulated release of the inflammatory chemokine IL-8 (p < 0.04) in cells cultured from subjects with ASD but not in cells from TD controls. These data suggest that in vitro exposure of PBMC to BDE-47 affects cell cytokine production in a pediatric population. Moreover, PBMC from the ASD subjects were differentially affected when compared with the TD controls suggesting a biological basis for altered sensitivity to BDE-47 in the ASD population.

AB - Autism spectrum disorders (ASD) are complex neurodevelopmental disorders that manifest in childhood. Immune dysregulation and autoimmune reactivity may contribute to the etiology of ASD and are likely the result of both genetic and environmental susceptibilities. A common environmental contaminant, 2,2′,4,4′-tetrabrominated biphenyl (BDE-47), was tested for differential effects on the immune response of peripheral blood mononuclear cells (PBMC) isolated from children with ASD (n = 19) and age-matched typically developing controls (TD, n = 18). PBMC were exposed in vitro to either 100 nM or 500 nM BDE-47, before challenge with bacterial lipopolysaccharide (LPS), an innate immune activator, with resultant cytokine production measured using the Luminex™ multiplex platform. The cytokine responses of LPS stimulated PBMC from ASD and TD subjects diverged in the presence of 100 nM BDE. For example, cells cultured from the TD group demonstrated significantly decreased levels of the cytokines IL-12p40, GM-CSF, IL-6, TNFα, and the chemokines MIP-1α and MIP-1β following LPS stimulation of PBMC pretreated with 100 nM BDE-47 compared with samples treated with vehicle control (p < 0.05). In contrast, cells cultured from subjects with ASD demonstrated an increased IL-1β response to LPS (p = 0.033) when pretreated with 100 nM BDE-47 compared with vehicle control. Preincubation with 500 nM BDE-47 significantly increased the stimulated release of the inflammatory chemokine IL-8 (p < 0.04) in cells cultured from subjects with ASD but not in cells from TD controls. These data suggest that in vitro exposure of PBMC to BDE-47 affects cell cytokine production in a pediatric population. Moreover, PBMC from the ASD subjects were differentially affected when compared with the TD controls suggesting a biological basis for altered sensitivity to BDE-47 in the ASD population.

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