Elevation of Tumor Necrosis Factor-Alpha in Cerebrospinal Fluid of Autistic Children

Chez, Michael G.; Dowling, Tim; Patel, Pikul B.; Khanna, Pavan; Kominsky, Matt

doi:10.1016/j.pediatrneurol.2007.01.012

Cited by 286 publications

(176 citation statements)

References 14 publications

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“…22 Both intrauterine inflammation and fetal brain inflammation are implicated in the development of ASD. [23][24][25] Diabetes also can lead to hyperglycemia. Maternal hyperglycemia triggers fetal hyperinsulinemia and increased oxygen consumption, inducing chronic intrauterine fetal tissue hypoxia.…”

Section: Figurementioning

confidence: 99%

The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities

Li¹,

Fallin²,

Riley³

et al. 2016

Pediatrics

244

200

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Section: Figurementioning

confidence: 99%

The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities

Li¹,

Fallin²,

Riley³

et al. 2016

Pediatrics

244

200

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“…13,15,17,22,53 Maternal transfer of immune dysregulation also is inferred by the fact that 47 of 100 mothers with serum auto-antibodies (especially at the 37 kD site) had offspring diagnosed with regressive cases of autism. 30,48 This evidence suggests that mothers positive for autoantibodies have almost a 50% chance of having children with the specific regressive phenotype of autism, indicating a potential delay from in utero exposure to clinical onset.…”

Section: Human Evidence Of Ongoing Atypical Inflammatory Responsementioning

confidence: 99%

“…Elevation, particularly of interleukin-6 and also of other pro-inflammatory markers in the frontal cingulated cortex and CSF, has been described by Vargas et al 17 Patients with regressive autism studied between pre-school age and 12 years old have been shown to have elevated CSF:serum ratios of TNF-␣, interleukin (IL)-1␤, IL-6, and IL 13. 53 Elevation of inflammatory cytokines offers potential therapeutic targets with agents that inhibit cytokine elevations, the use of anti-inflammatory cytokines (such as IL-10), stem cell therapy to re-regulate cytokine dysfunction, and designer drugs of the future that are modeled after these mechanisms. There is still much research to be done to be able to confirm these hopeful clues and observations that play a role in the etiology of autism, especially in patients with immune-associated risk factors or regression-type disease.…”

Section: Human Evidence Of Ongoing Atypical Inflammatory Responsementioning

confidence: 99%

“…53 A more recent, open-label trial of six boys with autistic regression and elevated CSF/serum cytokine profiles looked at treatment using 2.5 mg of lenalidomide per day for 12 weeks. 80 Lenalidomide (Revlimid; Celgene Corporation, Summit, NJ) is a derivative of thalidomide introduced in 2004, which was initially intended as a treatment for multiple myeloma.…”

Section: Treatment Of Cytokine Abnormalitiesmentioning

confidence: 99%

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Immune Therapy in Autism: Historical Experience and Future Directions with Immunomodulatory Therapy

Chez

Guido-Estrada

2010

Neurotherapeutics

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Summary: Autism affects 1 in 110 new births, and it has no single etiology with uniform agreement. This has a significant impact on the quality of life for individuals who have been diagnosed with autism. Although autism has a spectrum quality with a shared diagnosis, it presents a uniquely different clinical appearance in each individual. Recent research of suspected immunological factors have provided more support for a probable immunological process or for processes that may play a role in the acquisition of an autistic condition. These factors include prenatal, genetic, and postnatal findings, as well as the discovery of a dysfunctional chronic pro-inflammatory state in brain tissue and cerebrospinal fluid in subsets of autistic patients. These findings offer new theories that may lead to the development of disease modification or preventative therapeutic options in the near future. This article reviews prenatal, genetic, and observed immune aspects of the autism condition that may be risk factors in the presentation of the autistic clinical phenotype. Historical immune interventions in autism are reviewed and potential new therapies and interventions are discussed.

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“…Children with ASD have been noted to have increased levels of the pro-inflammatory cytokines MCP-1, interleukin (IL)-6, interferon-␣, INF-␥ and tumor necrosis factor-␣ (TNF-␣) in the brain or in the circulating blood. [15][16][17][18][19] Inflammation may mediate specific symptoms in ASD. For example, children with ASD and gastrointestinal symptoms were noted to have increased T-lymphocyte production of the pro-inflammatory cytokines, TNF-␣, and INF-␥ but decreased T-lymphocyte production of the anti-inflammatory cytokine, IL-10 in colonic, upper and lower small intestinal tissue.…”

Section: Inflammationmentioning

confidence: 99%

Improving the Prediction of Response to Therapy in Autism

Bent

Hendren

2010

Neurotherapeutics

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Summary: Autism is a heterogeneous disorder involving complex mechanisms and systems occurring at diverse times. Because an individual child with autism may have only a subset of all possible abnormalities at a specific time, it may be challenging to identify beneficial effects of an intervention in double-blind, randomized, controlled trials, which compare the mean responses to treatments. Beneficial effects in a small subset of children may be obscured by the lack of effect in the majority. We review the evidence for several potential model systems of biochemical abnormalities that may contribute to the etiology of autism, we describe potential biomarkers or treatment targets for each of these abnormalities, and we provide illustrative treatment trials using this methodology. Potential model systems include immune over and under reactivity, inflammation, oxidative stress, free fatty acid metabolism, mitochondrial dysfunction, and excitotoxicity. Including potential biomarkers and targeted treatments in clinical trials for autism provides a potential method for limiting the heterogeneity of enrolled subjects, which may improve the power of studies to identify beneficial effects of treatments while also improving the understanding of the disease.

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Elevation of Tumor Necrosis Factor-Alpha in Cerebrospinal Fluid of Autistic Children

Cited by 286 publications

References 14 publications

The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities

The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities

Immune Therapy in Autism: Historical Experience and Future Directions with Immunomodulatory Therapy

Improving the Prediction of Response to Therapy in Autism

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