Anti-inflammatory cytokines in autism spectrum disorders: A systematic review and meta-analysis

Background: In the search for the causes of autism spectrum disorders (ASD), inflammatory markers have emerged as potential candidates. The present meta-analysis was performed on studies examining circulating concentrations of anti-inflammatory cytokines in people with ASD compared with control subjects without ASD. Methods: We identified potentially eligible studies by systematically searching electronic databases from inception to February 2018. Results: Twenty-five studies with a total of 1754 participants (1022 patients with ASD and 732 control subjects) were included in the mate-analysis; 4 for interferon (IFN)-alpha, 9 for interleukin (IL)-1 receptor antagonist (Ra), 9 for IL-4, 6 for IL-5, 3 for IL-9, 14 for IL-10, 7 for IL-13, and 6 for transforming growth factor (TGF)-beta. We found a moderate decrease in plasma levels of IL-10 (SMD = 0.59) and a small decrease in serum levels of IL-1Ra (SMD = 0.25) in patients with ASD. On the contrary, serum IL-5 levels were slightly increased (SMD = 0.26) in these patients. We conducted meta-regression analyses to investigate the possible effect of moderatos on the effect size (ES) of difference in mean levels of IL-10. Difference in the mean age between patients and controls showed a negative influence on the ES and was able to explain about 0.4 of total between-study variance. In contrast, latitude exerted a positive effect on the ES and explained a lower proportion (0.1) of total between study variance. Conclusions: This meta-analysis provides evidence for the lower concentration of anti-inflammatory cytokines IL 10 and IL-1Ra in autistic patients compared with control subjects. Also, meta-regression analyses point to the interaction of latitude, age, and gender with peripheral alterations of associated anti-inflammatory cytokines.