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

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.