The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Elevation of Tumor Necrosis Factor-Alpha in Cerebrospinal Fluid of Autistic Children
Abstract
Recent reports implicating elevated cytokines in the central nervous system in a small number of patients studied with autism have reported clinical regression. These studies have not focused on tumor necrosis factor-alpha as a possible marker for inflammatory damage. A series of 10 children with autism had clinical evaluation of their serum and spinal fluid for inflammatory changes and possible metabolic disease as part of their neurological evaluation. Elevation of cerebrospinal fluid levels of tumor necrosis factor-alpha was significantly higher (mean = 104.10 pg/mL) than concurrent serum levels (mean = 2.78 pg/mL) in all of the patients studied. The ratio of the cerebrospinal fluid levels to serum levels averaged 53.7:1. This ratio is significantly higher than the elevations reported for other pathological states for which cerebrospinal fluid and serum tumor necrosis factor-alpha levels have been simultaneously measured. This observation may offer a unique insight into central nervous system inflammatory mechanisms that may contribute to the onset of autism and may serve as a potential clinical marker. More controlled study of this potentially important observation may prove valuable.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Moreover, increases in many cytokines and chemokines are observed in the brain and cerebrospinal fluid (CSF) of individuals with AD, in particular; interleukin (IL)-6, transforming growth factor beta 1 (TGFβ1), C-C motif ligand 2 (CCL2) and CCL17 in the cerebellum [73–76].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [74]
In the citing paper
“Furthermore, evidence suggests that children with ASD have elevated levels of pro-inflammatory cytokines including, interleukin 6 (IL–6), tumour necrosis factor alpha (TNF–α), and interferon gamma (IFN-γ) in different tissues [3,4,5,6,7].”
From Vitamin D and Autism Spectrum Disorder: A Literature Review (2016) · cites this paper as [5]
In the citing paper
“Similarly, IFN-γ has been noted as increased in individuals with ASD,13, 16, 17, 61 and IFN-γ was increased in ASD and correlated with C disporicum and C tertium.”
From Distinct Microbiome-Neuroimmune Signatures Correlate With Functional Abdominal Pain in Children With Autism Spectrum Disorder (2017) · cites this paper as [17]
In the citing paper
“Furthermore, increased IL6 has been seen in clinical cohorts of ASD.13, 14, 17, 60”
From Distinct Microbiome-Neuroimmune Signatures Correlate With Functional Abdominal Pain in Children With Autism Spectrum Disorder (2017) · cites this paper as [17]
Citations
Cites
(1943) · The Nervous child · Cited by 8,870
Neuroglial activation and neuroinflammation in the brain of patients with autism
Vargas, D. L., Nascimbene, C., Krishnan, C., Zimmerman, A. W., & Pardo, C. A. (2005) · Annals of Neurology · doi:10.1002/ana.20315 · Cited by 2,149
Proinflammatory Cytokines and Early Neurological Worsening in Ischemic Stroke
Vila, N., Castillo, J., Dávalos, A., & Chamorro, Á. (2000) · Stroke · doi:10.1161/01.str.31.10.2325 · Cited by 676
Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation
Nelson, K. B., Grether, J. K., Croen, L., Dambrosia, J. M., Dickens, B. F., Jelliffe‐Pawlowski, L. L., Hansen, R. L., & Phillips, T. M. (2001) · Annals of Neurology · doi:10.1002/ana.1024 · Cited by 434
Actions of TNF‐α on glutamatergic synaptic transmission in the central nervous system
Pickering, M., Cumiskey, D., & O'Connor, J. J. (2005) · Experimental Physiology · doi:10.1113/expphysiol.2005.030734 · Cited by 421
Cerebrospinal Fluid and Serum Markers of Inflammation in Autism
Zimmerman, A. W., Jyonouchi, H., Comi, A. M., Connors, S. L., Milstien, S., Varsou, A., & Heyes, M. P. (2005) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2005.03.014 · Cited by 300
Antibodies to Myelin Basic Protein in Children with Autistic Behavior
Singh, V. K., Warren, R. P., Odell, J. D., Warren, W. L., & Cole, P. (1993) · Brain, Behavior, and Immunity · doi:10.1006/brbi.1993.1010 · Cited by 274
Connolly, A. M., Chez, M. G., Streif, E. M., Keeling, R. M., Golumbek, P. T., Kwon, J. M., Riviello, J. J., Robinson, R., Neuman, R. J., & Deuel, R. K. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.07.004 · Cited by 265
Self-citationSerum autoantibodies to brain in Landau-Kleffner variant, autism, and other neurologic disorders
Connolly, A. M., Chez, M. G., Pestronk, A., Arnold, S. T., Mehta, S., & Deuel, R. K. (1999) · The Journal of Pediatrics · doi:10.1016/s0022-3476(99)70248-9 · Cited by 236
Self-citationShiozaki, T., Hayakata, T., Tasaki, O., Hosotubo, H., Fuijita, K., Mouri, T., Tajima, G., Kajino, K., Nakae, H., Tanaka, H., et al. (2005) · Shock · doi:10.1097/01.shk.0000161385.62758.24 · Cited by 152
Cited by
Sorted by citations
Items 301–315 of 315
Spectrum of Neurodegeneration in Autism Spectrum Disorder
Rani, K. (2022) · IGI Global eBooks · doi:10.4018/978-1-6684-5360-5.ch019
An Immune Rat Model of Autism: Does Environmental Enrichment Alter Higher Social Functioning?
Wilkin-Krug, L. C. M. (2021) · Open Access Victoria University of Wellington | Te Herenga Waka (Figshare) · doi:10.26686/wgtn.14635356.v1
Reber, M. E. (2012) · Cambridge University Press eBooks · doi:10.1017/cbo9780511978616.007
Olofinnade, A. T., Onaolapo, A. Y., & Onaolapo, O. J. (2024) · Adolescent Psychiatry · doi:10.2174/0122106766307803240819111607
Rudroff, T. (2025) · NeuroSci · doi:10.3390/neurosci6030080
“Importantly, interleukin-10 levels in recovered children typically remain within normal ranges or show compensatory elevation, contrasting sharply with the persistent deficiency observed in both Long COVID and autism [83,84].”
The Janus face of NK cells in neurodevelopment
Bian, Q., & Fu, B. (2025) · Trends in Immunology · doi:10.1016/j.it.2025.10.001
Chintalapally, S., Rajanala, K., & Upadhyay, A. K. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1655348
Zimmerman, A. W., Singh, K., Connors, S. L., Liu, H., Panjwani, A. A., Lee, L.-C., Diggins, E., Foley, A., Melnyk, S., Singh, I. N., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14677015
Additional file 1 of Adiponectin blood levels and autism spectrum disorders: a systematic review
Ali, M., Kamran, M., Talha, M., & Shad, M. U. (2024) · Figshare · doi:10.6084/m9.figshare.26675237
Paraschivescu, C. (2019) · theses.fr (ABES) · doi:10.70675/0de24a19z64d3z4a48z9f05z8dbe30d63fdf
Jiang, J., Yang, L., Wang, B., Hua, R., & Wu, D. (2026) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2026.04.007
“Notably, Chez et al. detected elevated TNF-α in the cerebro-spinal fluid (CSF) of autistic children (Chez et al., 2007), suggesting that compartmentalized fluid measures may more directly capture localized neuroinflammatory processes, whereas peripheral blood levels are more susceptible to systemic…”
Shahraki, Z. F., Noori, A., Amini-Khoei, H., Yazdanpanahi, N., & Fatemi, M. (2026) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2026.2702428
“Previous studies have been reported boosted inflammatory activity in children with autism, which evidenced by increase in level of pro-inflammatory biomarkers in their blood, cerebrospinal fluid and brain samples (Chez et al. 2007; Xiaohong Li et al. 2009; Xu et al. 2015).”
Gabr, R. I. (2026) · Developmental Neurobiology · doi:10.1002/dneu.70063
“Elevated levels of interleukin-1 β , interleukin-6, tumor necrosis factor-α , interferon-γ , and several chemokines have been associated with symptom severity, developmental regression, and cognitive impairment in selected cohorts (Chez et al. 2007 ; Rodriguez and Kern 2011 ).”
Fadini, C. C. (2013) · Americanae (AECID Library)
Effect of the Ketogenic Diet on Behavioral Symptoms of Autism in the Poly(IC) Mouse Model
Slade, S. L. (2015) · Trinity College Digital Repository (Trinity College, Hartford CT)
Metadata
- Authors
- Chez, M. G., Dowling, T., Patel, P. B., Khanna, P., & Kominsky, M.
- Affiliations
- Sutter Health (US)
- Illinois State University (US)
- Rosalind Franklin University of Medicine and Science (US)
- Corresponding author
- Chez, Michael G.
- ORCID
- Chez, Michael G.
- Venue
- Pediatric Neurology
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 36
- Issue
- 6
- Pages
- 361-365
- ISSN
- 0887-8994 (ISSN-L)
- OpenAlex
- W2063547860
- Cited by
- 317
- References
- 16
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 20 · 2023: 10 · 2022: 21 · 2021: 22 · 2020: 19 · 2019: 16 · 2018: 24 · 2017: 15 · 2016: 21 · 2015: 17 · 2014: 15 · 2013: 21 · 2012: 18
- FWCI
- 7.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pediatric Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- TNF-α, cerebrospinal fluid, autism spectrum disorder, cytokines, neuroinflammation, biomarkers
- MeSH terms
- Autistic Disorder, Central Nervous System, Child, Child, Preschool, Encephalitis, Female, Humans, Infant, Male, Tumor Necrosis Factor-alpha, Biomarkers, Early Diagnosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
