Journal of Molecular Neuroscience

, Volume 61, Issue 1, pp 1–7 | Cite as

Cytokine Profile in Autism Spectrum Disorders in Children

  • Vesna Bryn
  • Hans Christian Dalsbotten Aass
  • Ola H. Skjeldal
  • Jørn Isaksen
  • Ola Didrik Saugstad
  • Heidi Ormstad


The pathogenesis of autism spectrum disorders (ASD) is not completely understood, but there is evidence of associations with altered immune responses. The aim of this study was to determine the serum levels of various cytokines in children with ASD and in healthy controls, in order to determine their role in ASD and its diagnostic subgroups. Sixty-five ASD patients were enrolled from an epidemiological survey in Norway, of which 30 were diagnosed with childhood autism, 16 with Asperger syndrome, 12 with atypical autism, 1 with Rett syndrome, and 6 with another ASD diagnosis. The serum levels of 12 cytokines were measured in all of the patients and in 30 healthy children. The cytokine levels did not differ significantly between the ASD group and the healthy controls. However, the interleukin-8 (IL-8) level was significantly higher (6.82 vs 4.58 pg/ml, p = 0.017) while that of IL-10 was significantly lower (2.24 vs 6.49 pg/ml, p = 0.009) in patients with childhood autism than in controls. Furthermore, the IL-8 level was significantly higher in childhood autism than in Asperger syndrome (6.82 vs 4.05 pg/ml, p = 0.013). Our study shows that the cytokine profile of children diagnosed with ASD, regardless of the subdiagnosis, does not differ from healthy controls. However, differentiation into different diagnostic subgroups reveals significantly different levels of IL-8 and IL-10. This indicates that different mechanisms may underlie the different ASD subdiagnoses. Future research into the pathophysiological mechanisms of ASD should pay more attention to the different subdiagnoses of ASD.


Cytokine profile Autism spectrum disorders 



The authors gratefully acknowledge the assistance of pediatrician Pernille Tryli, diagnostic teams at the Departments of Habilitation at Lillehammer and Ottestad, and laboratory personnel in the hospitals at Lillehammer, Gjøvik, and Elverum. The study was supported by Innlandet Hospital research foundation.

Compliance with Ethical Standards

Written statements of informed consent were obtained from the parents before any child (ASD or control) was included in the project. The regional Committee for Research Ethics (REK) provided approval for the study to be performed.

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. Ashwood P et al (2011a) Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun 25:40–5CrossRefPubMedGoogle Scholar
  2. Ashwood P et al (2011b) Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders. J Neuroimmunol 232:196–9CrossRefPubMedGoogle Scholar
  3. Atladottir HO et al (2009) Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics 124:687–94CrossRefPubMedGoogle Scholar
  4. Baird G et al (2006) Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP). Lancet 368:210–5CrossRefPubMedGoogle Scholar
  5. Bauer S, Kerr BJ, Patterson PH (2007) The neuropoietic cytokine family in development, plasticity, disease and injury. Nat Rev Neurosci 8:221–32CrossRefPubMedGoogle Scholar
  6. Braunschweig D, Van de Water J (2012) Maternal autoantibodies in autism. Arch Neurol 69:693–9CrossRefPubMedPubMedCentralGoogle Scholar
  7. Braunschweig D et al (2008) Autism: maternally derived antibodies specific for fetal brain proteins. Neurotoxicology 29:226–31PubMedGoogle Scholar
  8. Brown AS (2012) Epidemiologic studies of exposure to prenatal infection and risk of schizophrenia and autism. Dev Neurobiol 72:1272–6CrossRefPubMedPubMedCentralGoogle Scholar
  9. Coleman M, Gillberg C, Gillberg, C.B.o.t.a.s (2012). The autisms, Vol., Oxford University Press, New York; OxfordGoogle Scholar
  10. Comi AM et al (1999) Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism. J Child Neurol 14:388–94CrossRefPubMedGoogle Scholar
  11. Cordeiro CN, Tsimis M, Burd I (2015) Infections and brain development. Obstet Gynecol Surv 70:644–55CrossRefPubMedPubMedCentralGoogle Scholar
  12. Croen LA et al (2005) Maternal autoimmune diseases, asthma and allergies, and childhood autism spectrum disorders: a case–control study. Arch Pediatr Adolesc Med 159:151–7CrossRefPubMedGoogle Scholar
  13. Croen LA et al (2008) Maternal mid-pregnancy autoantibodies to fetal brain protein: the early markers for autism study. Biol Psychiatry 64:583–8CrossRefPubMedPubMedCentralGoogle Scholar
  14. Croonenberghs J et al (2002) Activation of the inflammatory response system in autism. Neuropsychobiology 45:1–6CrossRefPubMedGoogle Scholar
  15. Dantzer R (2004) Cytokine-induced sickness behaviour: a neuroimmune response to activation of innate immunity. Eur J Pharmacol 500:399–411CrossRefPubMedGoogle Scholar
  16. Emanuele E et al (2010) Low-grade endotoxemia in patients with severe autism. Neurosci Lett 471:162–5CrossRefPubMedGoogle Scholar
  17. Fombonne E (2009) Epidemiology of pervasive developmental disorders. Pediatr Res 65:591–8CrossRefPubMedGoogle Scholar
  18. Gesundheit B et al (2013) Immunological and autoimmune considerations of autism spectrum disorders. J Autoimmun 44:1–7CrossRefPubMedGoogle Scholar
  19. Isaksen J et al (2012) Observed prevalence of autism spectrum disorders in two Norwegian counties. Eur J Paediatr Neurol 16:592–8CrossRefPubMedGoogle Scholar
  20. Isaksen J et al (2013) Children with autism spectrum disorders—the importance of medical investigations. Eur J Paediatr Neurol 17:68–76CrossRefPubMedGoogle Scholar
  21. Jarskog LF et al (1997) Cytokine regulation of embryonic rat dopamine and serotonin neuronal survival in vitro. Int J Dev Neurosci 15:711–6CrossRefPubMedGoogle Scholar
  22. Levy SE, Mandell DS, Schultz RT (2009) Autism Lancet 374:1627–38CrossRefPubMedGoogle Scholar
  23. Masi A, Quintana, DS, (2015). Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis. 20, 440–6Google Scholar
  24. Mead J, Ashwood P (2015) Evidence supporting an altered immune response in ASD. Immunol Lett 163:49–55CrossRefPubMedGoogle Scholar
  25. Meyer U, Feldon J, Yee BK (2009) A review of the fetal brain cytokine imbalance hypothesis of schizophrenia. Schizophr Bull 35:959–72CrossRefPubMedGoogle Scholar
  26. Mouridsen SE et al (2007) Autoimmune diseases in parents of children with infantile autism: a case–control study. Dev Med Child Neurol 49:429–32CrossRefPubMedGoogle Scholar
  27. Mousa A et al (1999) Human first trimester forebrain cells express genes for inflammatory and anti-inflammatory cytokines. Cytokine 11:55–60CrossRefPubMedGoogle Scholar
  28. Napolioni V et al (2013) Plasma cytokine profiling in sibling pairs discordant for autism spectrum disorder. J Neuroinflammation 10:38CrossRefPubMedPubMedCentralGoogle Scholar
  29. Nawa H, Takei N (2006) Recent progress in animal modeling of immune inflammatory processes in schizophrenia: implication of specific cytokines. Neurosci Res 56:2–13CrossRefPubMedGoogle Scholar
  30. Nordahl CW et al (2013) Maternal autoantibodies are associated with abnormal brain enlargement in a subgroup of children with autism spectrum disorder. Brain Behav Immun 30:61–5CrossRefPubMedPubMedCentralGoogle Scholar
  31. Onore C, Careaga M, Ashwood P (2012) The role of immune dysfunction in the pathophysiology of autism. Brain Behav Immun 26:383–92CrossRefPubMedGoogle Scholar
  32. Persico AM, Bourgeron T (2006) Searching for ways out of the autism maze: genetic, epigenetic and environmental clues. Trends Neurosci 29:349–58CrossRefPubMedGoogle Scholar
  33. Rogers SJ (2004) Developmental regression in autism spectrum disorders. Ment Retard Dev Disabil Res Rev 10:139–43CrossRefPubMedGoogle Scholar
  34. Rose D, Ashwood P (2014) Potential cytokine biomarkers in autism spectrum disorders. Biomark Med 8:1171–81CrossRefPubMedGoogle Scholar
  35. Singer HS et al (2008) Antibodies against fetal brain in sera of mothers with autistic children. J Neuroimmunol 194:165–72CrossRefPubMedGoogle Scholar
  36. Singh VK et al (1991) Changes of soluble interleukin-2, interleukin-2 receptor, T8 antigen, and interleukin-1 in the serum of autistic children. Clin Immunol Immunopathol 61:448–55CrossRefPubMedGoogle Scholar
  37. Spence SJ, Schneider MT (2009) The role of epilepsy and epileptiform EEGs in autism spectrum disorders. Pediatr Res 65:599–606CrossRefPubMedPubMedCentralGoogle Scholar
  38. Suzuki K et al (2011) Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders. PLoS One 6, e20470CrossRefPubMedPubMedCentralGoogle Scholar
  39. Sweeten TL et al (2004) High nitric oxide production in autistic disorder: a possible role for interferon-gamma. Biol Psychiatry 55:434–7CrossRefPubMedGoogle Scholar
  40. Taylor LE, Swerdfeger AL, Eslick GD (2014) Vaccines are not associated with autism: an evidence-based meta-analysis of case–control and cohort studies. Vaccine 32:3623–9CrossRefPubMedGoogle Scholar
  41. Xu N, Li X, Zhong Y (2015) Inflammatory cytokines: potential biomarkers of immunologic dysfunction in autism spectrum disorders. Mediat Inflamm 2015:531518Google Scholar
  42. Zimmerman AW et al (2005) Cerebrospinal fluid and serum markers of inflammation in autism. Pediatr Neurol 33:195–201CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of PediatricsInnlandet Hospital TrustLillehammerNorway
  2. 2.Department of Medical BiochemistryOslo University HospitalOsloNorway
  3. 3.Gillberg Neuropsychiatry CentreUniversity of GothenburgGothenburgSweden
  4. 4.Department of HabilitationInnlandet Hospital TrustLillehammerNorway
  5. 5.Pediatric Research Institute, RikshospitaletOslo University HospitalOsloNorway
  6. 6.Faculty of Health SciencesUniversity College of Southeast NorwayDrammenNorway

Personalised recommendations