Interleukin-1 β /Interleukin10 Ratio Produced by Monocytes as a Biomarker of Neuroinflammation in Autism

Objective: Innate immune abnormalities have been frequently reported in children with autism spectrum disorders (ASD), but a role of innate immunity in ASD is not well understood. This study explored a possible role of innate immunity in ASD clinical features and co-morbidities.Methods: Purified peripheral blood monocytes (PBMo) from ASD (N=125) and non-ASD (N=36) subjects were cultured overnight with or without stimulants of innate immunity, and production of pro-inflammatory and counter-regulator cytokines were assessed. Behavioral symptoms were assessed by aberrant behavioral checklist (ABC) at the time of PBMo sampling.Results: ASD PBMo revealed highly variable IL-1β/IL-10 ratios, in contrast to a tight range of IL-1β/IL-10 ratios in non-ASD control cells. There was no association between cytokine levels or IL-1β/IL-10 ratios and ABC subscale scores when ASD data was analyzed, as a whole. However, when ASD data was separated into high, low, or normal (equivalent to controls) IL-1β/IL-1 ratio groups, IL-1β levels were positively associated with stereotypy in the high ratio group. In contrast, IL-1β and IL-10 levels were negatively associated with irritability, lethargy, and hyperactivity in the normal ratio group. The low ratio group revealed a negative association between IL-1β levels and lethargy. When longitudinal changes in cytokine production from PBMo were studied in selected ASD subjects, fluctuating ratios were found in ASD subjects with deviated (high or low) IL-1β/IL-10 ratios, but ratios remained stable in ASD subjects with normal ratios. ASD subjects with deviated ratios were found to have higher frequencies of non-IgE mediated food allergy (NFA) (p<0.05) and seizure disorder (p<0.01) than those with normal ratios.Conclusion: IL-1β and IL-10 produced by innate immune responses play crucial roles in the neuroimmune network. Thus the deviated (high or low) IL-1β/IL-10 ratio from ASD monocytes may be a promising candidate biomarker for assessing changes of neuroimmune regulations and risk of comorbidities (NFA and seizure disorders) in ASD.