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Vol. 51, No. 2, 2005
Issue release date: March 2005
Section title: Original Paper
Neuropsychobiology 2005;51:77–85
(DOI:10.1159/000084164)

Dysregulated Innate Immune Responses in Young Children with Autism Spectrum Disorders: Their Relationship to Gastrointestinal Symptoms and Dietary Intervention

Jyonouchi H. · Geng L. · Ruby A. · Zimmerman-Bier B.
Department of Pediatrics, New Jersey Medical School, UMDNJ, Newark, N.J., USA

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: 3/17/2005

Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 4

ISSN: 0302-282X (Print)
eISSN: 1423-0224 (Online)

For additional information: http://www.karger.com/NPS

Abstract

Objective: Our previous study indicated an association between cellular immune reactivity to common dietary proteins (DPs) and excessive proinflammatory cytokine production with endotoxin (lipopolysaccharide, LPS), a major stimulant of innate immunity in the gut mucosa, in a subset of autism spectrum disorder (ASD) children. However, it is unclear whether such abnormal LPS responses are intrinsic in these ASD children or the results of chronic gastrointestinal (GI) inflammation secondary to immune reactivity to DPs. This study further explored possible dysregulated production of proinflammatory and counter-regulatory cytokines with LPS in ASD children and its relationship to GI symptoms and the effects of dietary intervention measures. Methods: This study includes ASD children (median age 4.8 years) on the unrestricted (n = 100) or elimination (n = 77) diet appropriate with their immune reactivity. Controls include children with non-allergic food hypersensitivity (NFH; median age 2.9 years) on the unrestricted (n = 14) or elimination (n = 16) diet, and typically developing children (median age 4.5 years, n = 13). The innate immune responses were assessed by measuring production of proinflammatory (TNF-α, IL-1β, IL-6, and IL-12) and counter-regulatory (IL-1ra, IL-10, and sTNFRII) cytokines by peripheral blood mononuclear cells (PBMCs) with LPS. The results were also compared to T-cell responses with common DPs and control T-cell mitogens assessed by measuring T-cell cytokine production. Results: ASD and NFH PBMCs produced higher levels of TNF-α with LPS than controls regardless of dietary interventions. However, only in PBMCs from ASD children with positive gastrointestinal (GI(+)) symptoms, did we find a positive association between TNF-α levels produced with LPS and those with cow’s milk protein (CMP) and its major components regardless of dietary interventions. In the unrestricted diet group, GI(+) ASD PBMCs produced higher IL-12 than controls and less IL-10 than GI(–) ASD PBMCs with LPS. GI(+) ASD but not GI(–) ASD or NFH PBMCs produced less counter-regulatory cytokines with LPS in the unrestricted diet group than in the elimination diet group. There was no significant difference among the study groups with regard to cytokine production in responses to T-cell mitogens and other recall antigens. Conclusion: Our results revealed that there are findings limited to GI(+) ASD PBMCs in both the unrestricted and elimination diet groups. Thus our findings indicate intrinsic defects of innate immune responses in GI(+) ASD children but not in NFH or GI(–) ASD children, suggesting a possible link between GI and behavioral symptoms mediated by innate immune abnormalities.


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: 3/17/2005

Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 4

ISSN: 0302-282X (Print)
eISSN: 1423-0224 (Online)

For additional information: http://www.karger.com/NPS


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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