Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Dec 2:8:63.
doi: 10.1186/s13229-017-0176-2. eCollection 2017.

Cytokine levels and associations with symptom severity in male and female children with autism spectrum disorder

Anne Masi  1 , Edmond J Breen  2 , Gail A Alvares  3   4 , Nicholas Glozier  1 , Ian B Hickie  1 , Anna Hunt  3 , Jennie Hui  5   6   7 , John Beilby  5   6 , David Ravine  5   6 , John Wray  8 , Andrew J O Whitehouse  3   4 , Adam J Guastella  1
Affiliations

Cytokine levels and associations with symptom severity in male and female children with autism spectrum disorder

Anne Masi et al. Mol Autism. .

Abstract

Background: Autism spectrum disorders (ASDs) are complex, pervasive, and heterogeneous neurodevelopmental conditions with varying trajectories, significant male bias and largely unknown etiology. However, an understanding of the biological mechanisms driving pathophysiology is evolving. Immune system aberrations, as identified through cytokine profiles, are believed to have a role in ASD. Altered cytokine levels may facilitate identification of ASD subtypes as well as provide biological markers of response to effective treatments. Research exploring the relationship between cytokine profiles and ASD symptoms is, however, in its infancy. The objective of this study was to explore relationships between cytokine levels and the severity of ASD and other clinical traits.

Methods: Multiplex assay techniques were used to measure levels of 27 cytokines in plasma samples from a cohort of 144 children diagnosed with ASD.

Results: Overall, results showed a significant negative association between platelet-derived growth factor (PDGF)-BB, and the severity of ASD symptoms. Furthermore, a significant interaction with sex suggested a different immune profile for females compared to males. ASD symptom severity was negatively associated with levels of 4 cytokines, IL-1β, IL-8, MIP-1β, and VEGF, in females, but not in males.

Conclusions: Results of the present study suggest that an altered cytokine response or profile is associated with the severity of ASD-related symptoms, with sex a potential modifier of this relationship. Further research in larger populations which recognizes the importance of sex comparisons and longitudinal assessments are now required to extend and further describe the role of the immune system in ASD.

Keywords: Autism spectrum disorder; Behavior; Cytokine; Pediatric; Severity.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

Ethics approval was granted by the Human Ethics Committee at Princess Margaret Hospital for Children in Perth, Western Australia, and informed consent was provided by the primary caregiver prior to participation.

Consent for publication

Not applicable.

Competing interests

Author IBH is a Commissioner in Australia’s new National Mental Health Commission from 2012. He is the Co-Director, Health and Policy at the Brain and Mind Centre which operates two early-intervention youth services under contract to headspace. IBH has led a range of community-based and pharmaceutical industry-supported depression awareness and education and training programs. He has led projects for health professionals and the community supported by governmental, community agency, and pharmaceutical industry partners (Wyeth, Eli Lily, Servier, Pfizer, AstraZeneca) for the identification and management of depression and anxiety. He has received honoraria for presentations of his own work at educational seminars supported by a number of non-government organizations and the pharmaceutical industry (including Servier, Pfizer, AstraZeneca, and Eli Lilly). He is a member of the Medical Advisory Panel for Medibank Private and also a Board Member of Psychosis Australia Trust. He leads an investigator-initiated study of the effects of agomelatine on circadian parameters (supported in part by Servier) and has participated in a multicenter clinical trial of the effects of agomelatine on sleep architecture in depression and a Servier-supported study of major depression and sleep disturbance in primary care settings.

The remaining authors declare they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Optimal network graphs representing cytokine correlations separated for sex. Each node represents a cytokine, and each edge represents a Spearman’s correlation between two cytokines. Green edges indicate positive correlations and red edges represent negative correlations. The width of the edge corresponds to the absolute value of the correlation: the higher the correlation, the thicker and more saturated is the edge. Node abbreviations: B.F basic fibroblast growth factor, Etx eotaxin, G.C granulocyte colony-stimulating factor, GM granulocyte macrophage colony-stimulating factor, IFN interferon-gamma, IL interleukin, IL.1B 1 beta, IL.1r IL-1 receptor antagonist, IL.12 IL-12p70, IL.17 IL-17A, IP interferon gamma-inducible protein 10, MCP monocyte chemotactic protein-1, MIP.1a macrophage inflammatory protein-1 alpha, MIP.1b macrophage inflammatory protein-1 beta, PDG platelet-derived growth factor-BB, RAN regulated on activation, normal T cell expressed and secreted, TNF tumor necrosis factor-alpha, VEG vascular endothelial growth factor
See this image and copyright information in PMC

References

    1. CDC Prevalence of autism spectrum disorder among children aged 8 years—autism and developmental disabilities monitoring network, 11 sites, United States, 2010. Morbidity and Mortality Weekly Report: Surveillance Summaries. 2014;63:1–14. - PubMed
    1. American Psychiatric Association . Diagnostic and statistical manual of mental disorders. 5. Washington, DC: American Psychiatric Press; 2013.
    1. Howlin P, Goode S, Hutton J, Rutter M. Adult outcome for children with autism. J Child Psychol Psychiatry. 2004;45:212–229. doi: 10.1111/j.1469-7610.2004.00215.x. - DOI - PubMed
    1. Szatmari P, Georgiades S, Duku E, et al. Developmental trajectories of symptom severity and adaptive functioning in an inception cohort of preschool children with autism spectrum disorder. JAMA Psychiatry. 2015;72:276–283. doi: 10.1001/jamapsychiatry.2014.2463. - DOI - PubMed
    1. Fein D, Barton M, Eigsti IM, Kelley E, Naigles L, Schultz RT, Stevens M, Helt M, Orinstein A, Rosenthal M. Optimal outcome in individuals with a history of autism. J Child Psychol Psychiatry. 2013;54:195–205. doi: 10.1111/jcpp.12037. - DOI - PMC - PubMed