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.
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“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]
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Aldossari, A. A., Ansari, M. A., Nadeem, A., Attia, S. M., Bakheet, S. A., AL-Ayadhi, L. Y., Alanazi, M. M., Shahid, M., Alwetaid, M. Y., Hussein, M. H., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087475 · Cited by 13
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Neuropsychiatric disorders: An immunological perspective
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“Elevated levels of chemokines have been detected in the brains and cerebrospinal fluid (Chez et al., 2007; Wills et al., 2009) as well as the plasma (Ashwood et al., 2011a) of individuals with ASD, and this elevation correlated with more impaired behavior (Ashwood et al., 2011b).”
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Srivastava, V., & O’Reilly, C. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106202 · Cited by 11
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Smith, S. E. P., Hsiao, E. Y., & Patterson, P. H. (2010) · Springer eBooks · doi:10.1007/978-1-60327-921-5_7 · Cited by 12
“CSF from 10 autistic children Increased TNFa [ 77 ] CSF from 6 autistic children Increases in many cytokines, including IFNg, TGFb2 MCP-1 IL-8 [78]”
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Chen, S., Wang, J., Chen, X., Zhang, Y., Hong, Y., Zhuang, W., Huang, X., Kang, J., Ou, P., & Huang, L. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e37130 · Cited by 7
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Purushotham, S. S., Reddy, N. M. N., D’Souza, M. N., Choudhury, N. R., Ganguly, A., Gopalakrishna, N., Muddashetty, R. S., & Clement, J. P. (2022) · Experimental Brain Research · doi:10.1007/s00221-022-06448-x · Cited by 8
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Adiponectin blood levels and autism spectrum disorders: a systematic review
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“In this context, the anti-inflammatory role of adiponectin in suppressing proinflammatory cytokines, such as TNF-α, IL-6 [55, 56], and Interferon (IFN)-γ [56, 57], that are elevated in ASD [56, 58, 59].”
BackgroundNeurotoxic Brainstem Impairment as Proposed Threshold Event in Autistic Regression
McGinnis, W. R., Miller, V. M., AUDHYA, T. K., & Edelson, S. B. (2009) · CRC Press eBooks · doi:10.1201/9781420068870-c9 · Cited by 7
Inflammation and the Brain Disorders: A Review
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“Tumor necrosis factor-alpha (TNF-α ) is a pivotal mediator of inflammation and exhibits increased levels in the cerebrospinal fluid of individuals diagnosed with ASD [37].”
Alteration of Neurodevelopment and behavior by Maternal Immune Activation
Smith, S. E. P., & Patterson, P. H. (2008) · Springer eBooks · doi:10.1007/978-0-387-84851-8_7 · Cited by 7
“A 50-fold increase in TNFα levels was found in a study of cerebrospinal fluid (CSF) from ten autistic patients ( Chez et al., 2007 ).”
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“Proinflammatory cytokines have a predominantly central origin: the blood TNF-α level in autism is significantly lower than that in the cerebrospinal fluid [22].”
Chidambaram, S. B., Bhat, A., Mahalakshmi, A. M., Ray, B., Tuladhar, S., Sushmitha, B. S., Saravanan, B., Manivasagam, T., Thenmozhi, A. J., Essa, M. M., et al. (2020) · Advances in neurobiology · doi:10.1007/978-3-030-30402-7_20 · Cited by 6
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May lovastatin target both autism and epilepsy? A novel hypothesized treatment
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“Cerebrospinalfluid and serumTNFα levels are increased in autism and can be a clinical marker [15].”
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“45,46 These studies suggest that IL-6 plays a crucial role in mediating neurodevelopmental disorders in MIA offspring.”
Maternal immune dysregulation and autism spectrum disorder
Ramirez-Celis, A., Kim, D. H. J., & de Water, J. V. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-824421-0.00010-2 · Cited by 5
The Role of Inflammation in Autism Spectrum Disorder
Ferretti, C. J., & Hollander, E. (2015) · Current topics in neurotoxicity · doi:10.1007/978-3-319-13602-8_14 · Cited by 5
Redox/Methylation Theory and Autism
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Mitochondrial Dysfunction in Autistic Children and Oral Coenzyme Q10 Supplementation Treatment
Mousavinejad, E., & Ghaffari, M. A. (2016) · Autism - Open Access · doi:10.4172/2165-7890.1000189 · Cited by 5
“Recently, studies have reported that patient with ASD and who are treated with anti-inflammatory compounds showed the most improvement in social interaction and communication and decreased serum TNF-α and IL-6 levels [35,36].”
BackgroundDifferential T Cell Levels of Tumor Necrosis Factor Receptor-II in Children With Autism
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“There is no consensus explaining this observation, but there are high hopes that solving this puzzle may pave the way for new strategies in treatment of ASD [32-34].”
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Potential approaches and recent advances in biomarker discovery in autism spectrum disorders
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“Several studies have indeed reported pro-inflammatory cytokine patterns in CSF and blood ( Chez, Dowling, Patel, Khanna, & Kominsky, 2007; Croonenberghs, Bosmans, Deboutte, Kenis, & Maes, 2002; Jyonouchi, Sun, & Le, 2001; Molloy et al., 2006; Singh, 1996; Zimmerman et al., 2005).”
Understanding on Neuroimmunology in Autism Spectrum Disorder
Depino, A. M., & Robinson‐Agramonte, M. D. L. Á. (2015) · Springer eBooks · doi:10.1007/978-3-319-16321-5_9 · Cited by 3
The Role of Serotonin in Cortical Development: Implications for Autism Spectrum Disorder
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“In a study of children with ASD, the ratio of CSF to serum TNF-α was noticeably increased when investigating the inflammatory state of the central nervous system (Chez et al. 2007).”
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Morris, C. M., Pletnikov, M. V., Zimmerman, A. W., & Singer, H. S. (2008) · Humana Press eBooks · doi:10.1007/978-1-60327-489-0_14 · Cited by 3
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“Chez et al. identified increased TNF‐α levels in the cerebrospinal fluid of patients with ASD [61].”
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“Additionally, increased levels of interferon-ɣ , IL-8, MCP-1, TGF-β 2, and TNF-α have been re-ported in the CSF of ASD patients (Chez et al., 2007; Shen et al., 2020).”
Autism’s cancer connection: The anti-proliferation hypothesis and why it may matter
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“However, cerebrospinal fluid levels of TNF-a are also elevated in children with autism [87].”
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Hyperbaric Oxygen Treatment in Autism Spectrum Disorders
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“…) and TNF-α ; in addition to elevated proinflammatory Th17 cytokines (Masi et al., 2017a; Pardo et al., 2005; Masi et al., 2015; Masi et al., 2017b; Chez et al., 2007; Garbett et al., 2009; Abdallah et al., 2013; AL-Ayadhi and Mostafa, 2012; Croonenberghs et al., 2002; Li et al., 2009; Ricci et…”
Immune System Related Markers: Changes in childhood Neuropsychiatry Disorders Cause and Consequence
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REVIEW: PENYEBAB GANGGUAN AUTIS MELALUI JALUR NEUROINFLAMASI
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“The role of TNF-α as a neuromodulatory agent in brain development has also been described [7].”
Natroshvili, I., Gakharia, T., Bakhtadze, S., Natsvlishvili, T., & Khachapuridze, N. (2025) · Children · doi:10.3390/children12111488 · Cited by 1
“In ASD patients, abnormal cytokine levels have been observed in the peripheral blood [3,8], as well as reduced cytotoxic activity and elevated levels of proinflammatory cytokines such as interleukin 1 (IL-1) and tumor necrosis factor (TNF-1) [9,10].”
Perinatal Immune Activation and Risk of Autism
Theoharides, T. C., Angelidou, A., Alysandratos, K., Asadi, S., Francis, K., Lykouras, L., & Kalogeromitros, D. C. (2011) · InTech eBooks · doi:10.5772/17436 · Cited by 1
“For instance, TNF was high in the cerebrospinal fluid (CSF) (Chez et al., 2007), and IL-6 gene expression was increased in the brain (Li et al.”
BackgroundPossible Impact of Innate Immunity on Autism
Jyonouchi, H. (2009) · CRC Press eBooks · doi:10.1201/9781420068870-c13 · Cited by 1
Demirdöğen, E. Y., Akıncı, M. A., Bozkurt, A., Esmeray, Ö., Özgeriş, F. B., Kurt, N., & Yüce, N. (2024) · Research in Autism · doi:10.1016/j.rasd.2024.102327 · Cited by 1
Nosratiyan, N., Ghasemi‐Kasman, M., Pourghasem, M., Feizi, F., & Sadeghi, F. (2025) · Brain Sciences · doi:10.3390/brainsci15080798 · Cited by 1
“Clinical studies have reported elevated levels of pro-inflammatory cytokines such as IL-6, TNF-α , and IL-1 β in the plasma, blood mononuclear cells, serum, and cerebrospinal fluid (CSF) of autistic patients [4,5].”
Clinical Evaluations on the Diagnosis of Autism
Dobre, M., & Stoic, I. (2011) · InTech eBooks · doi:10.5772/17912 · Cited by 1
“were found to be in high concentrations in autism (Ashwood et al., 2006; Chez et al., 2007).”
Immune Dysfunction in Autism Spectrum Disorder
Malkova, N. V., & Hsiao, E. Y. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800109-7.00005-4 · Cited by 2
Malaria in Pregnancy: An Unrecognized Risk Factor for Neuropsychiatric Disease in Offspring?
Tran, V., Weckman, A. M., & Kain, K. C. (2016) · Pediatric Infectious Diseases Open Access · doi:10.21767/2573-0282.100016 · Cited by 1
“Consistent with this model, patients with ASD and schizophrenia often exhibit abnormal immunology, including increased levels of IL-6 and TNF in circulation and in cerebrospinal fluid, in adulthood [64,65].”
Ng, M., de Montigny, J., Ofner, M., & Do, M. (2017) · Promotion de la santé et prévention des maladies chroniques au Canada · doi:10.24095/hpcdp.37.1.01f · Cited by 1
Spectrum of Neurodegeneration in Autism Spectrum Disorder
Rani, K. (2018) · Advances in medical diagnosis, treatment, and care (AMDTC) book series · doi:10.4018/978-1-5225-5282-6.ch016 · Cited by 1
Ansari, M. A., Bakheet, S. A., AL-Ayadhi, L. Y., Khan, M. R., Attia, S. M., & Ahmad, S. F. (2019) · Research in Autism · doi:10.1016/j.rasd.2019.101500 · Cited by 1
Autism, Development and Neural Plasticity
Robinson‐Agramonte, M. D. L. Á., Fraguela, M. E. G., & Bergado, J. A. (2015) · Springer eBooks · doi:10.1007/978-3-319-16321-5_7 · Cited by 1
Kirsten, T. B. (2012) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.10.2012.tde-25072013-142030 · Cited by 1
Mott, M. C. (2011) · ThinkIR: The University of Louisville's Institutional Repository (University of Louisville) · doi:10.18297/etd/1016
Lawler, C. P., & Halladay, A. K. (2010) · Wiley eBooks · doi:10.1002/9780470917060.ch10
Immune System and Neurotrophic Factors in Autism
İşeri, E., & Güney, E. (2011) · InTech eBooks · doi:10.5772/21798
“It is put forward that TNF – alpha levels may be the indicator of possible inflammatory damage in autistic disorder (Chez et al. 2007).”
BackgroundA Whole-Body Systems Approach to ASD
Herbert, M. R. (2010)
Cytokine Polymorphisms in Autism
Crespo, F. A., Fernandez-Botrán, R., Tillquist, C. R., Sears, L. L., Mott, M. C., & Casanova, M. F. (2009) · CRC Press eBooks · doi:10.1201/9781420068870-c16
Association of MIF with Autism Spectrum Disorders
Kawiková, I., Leckman, J. F., Morer, Á., & Grigorenko, E. L. (2012) · WORLD SCIENTIFIC eBooks · doi:10.1142/9789814335362_0020
Paraoxonase 1 Status, Environmental Exposures, and Oxidative Stress in Autism Spectrum Disorders
Dronca, M., & Pașca, S. P. (2009) · CRC Press eBooks · doi:10.1201/9781420068870-c6
Deciphering the Risk Factors of Autism: Are We There Yet?
Nizam, R., & AlFadhli, S. M. (2016) · Journal of Biosciences and Medicines · doi:10.4236/jbm.2016.410007
“Supportively, increased levels of IL-6 and TNF have been reported in brain and cerebro spinal fluid of autistic patients respectively [16] [17].”
Serotonin in cortical development: implications for autism spectrum disorder
Höhmann, C. F., Lange, M. S., & Blue, M. E. (2020) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-444-64125-0.00046-3
A perinatal strategy to prevent autism
Das, U. N. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818466-0.00001-0
Maternal immune activation and preeclampsia
Azizkhanian, & Ida (2015)
Can bioactive lipids arachidonic and docosahexaenoic acids prevent autism and reduce its severity?
Das, U. N. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-85031-5.00020-7
CTRP3 as a novel biomarker in the plasma of Saudi children with autism
Alhakbany, M. A., AL-Ayadhi, L. Y., & El-Ansary, A. K. (2022) · PeerJ · doi:10.7717/peerj.12630
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
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