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
. 2021 Jul 2:12:670200.
doi: 10.3389/fpsyt.2021.670200. eCollection 2021.

Association of Peripheral Blood Levels of Cytokines With Autism Spectrum Disorder: A Meta-Analysis

Affiliations

Association of Peripheral Blood Levels of Cytokines With Autism Spectrum Disorder: A Meta-Analysis

Huaying Zhao et al. Front Psychiatry. .

Abstract

Background: Although increasing evidence suggests an association between alterations in peripheral cytokines and autism spectrum disorder (ASD), a consensus is lacking. To determine whether abnormal cytokine profiles in peripheral blood were associated with ASD, we performed this systemic review and meta-analysis. Methods: A systematic literature search was conducted through the Embase, PubMed, Web of Knowledge, PsycINFO, and Cochrane databases up to 4 June 2020. Clinical studies exploring the aberration of peripheral cytokines of autistic patients and controls were included in our meta-analysis. We pooled extracted data using fixed- or random-effects models based on heterogeneity tests with Comprehensive Meta-analysis software. We converted standardized mean differences to Hedges' g statistic to obtain the effect sizes adjusted for sample size. Subgroup analyses, sensitivity analyses, meta-regression, and publication bias tests were also carried out. Results: Sixty-one articles (326 studies) were included to assess the association between 76 cytokines and ASD. We conducted our meta-analysis based on 37 cytokines with 289 studies. Since there were fewer than three studies on any of the other 39 cytokines, we only provided basic information for them. The levels of peripheral IL-6, IL-1β, IL-12p70, macrophage migration inhibitory factor (MIF), eotaxin-1, monocyte chemotactic protein-1 (MCP-1), IL-8, IL-7, IL-2, IL-12, tumor necrosis factor-α (TNF-α), IL-17, and IL-4 were defined as abnormal cytokines in the peripheral blood of ASD patients compared with controls. The other 24 cytokines did not obviously change in ASD patients compared with the controls. Conclusions: The findings of our meta-analysis strengthen the evidence for an abnormal cytokine profile in ASD. These abnormal cytokines may be potential biomarkers for the diagnosis and treatment of ASD in the future.

Keywords: association; autism spectrum disorder; cytokines; plasma; serum.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of study identification.
Figure 2
Figure 2
Forest plot for the random-effects meta-analysis (IL-6).
Figure 3
Figure 3
Forest plot for the random-effects meta-analysis (IL-1β).
Figure 4
Figure 4
Forest plot for the fixed-effects meta-analysis (eotaxin-1).
Figure 5
Figure 5
Forest plot for the random-effects meta-analysis (MIF).
Figure 6
Figure 6
Forest plot for the random-effects meta-analysis (IL-12p70).
Figure 7
Figure 7
Forest plot for the fixed-effects meta-analysis (MCP1).
Figure 8
Figure 8
Forest plot for the random-effects meta-analysis (IL-8).
Figure 9
Figure 9
Forest plot for the fixed-effects meta-analysis (IL-7).

References

    1. Courchesne E, Pramparo T, Gazestani VH, Lombardo MV, Pierce K, Lewis NE. The ASD living biology: from cell proliferation to clinical phenotype. Mol Psychiatry. (2019) 24:88–107. 10.1038/s41380-018-0056-y - DOI - PMC - PubMed
    1. Hadwin JA, Lee E, Kumsta R, Cortese S, Kovshoff H. Cortisol awakening response in children and adolescents with autism spectrum disorder: a systematic review and meta-analysis. Evid Based Ment Health. (2019) 22:118–24. 10.1136/ebmental-2019-300098 - DOI - PMC - PubMed
    1. Hong MP, Erickson CA. Investigational drugs in early-stage clinical trials for autism spectrum disorder. Expert Opin Investig Drugs. (2019) 28:709–18. 10.1080/13543784.2019.1649656 - DOI - PubMed
    1. Edmiston E, Ashwood P, Van de Water J. Autoimmunity, autoantibodies, and autism spectrum disorder. Biol Psychiatry. (2017) 81:383–90. 10.1016/j.biopsych.2016.08.031 - DOI - PMC - PubMed
    1. Pangrazzi L, Balasco L, Bozzi Y. Oxidative stress and immune system dysfunction in autism spectrum disorders. Int J Mol Sci. (2020) 21:3293. 10.3390/ijms21093293 - DOI - PMC - PubMed

Publication types