An association between IL-1ß production and mitochondrial functions in patients with autism spectrum disorders (ASD)

Innate immune abnormalities and mitochondrial dysfunction are frequently reported in ASD subjects, indicating a possible association between immune-mediated inflammation and mitochondrial dysfunction in ASD. Inflammatory cytokine such as IL-1ß generated by innate immune cells affect mitochondrial functions. In 71 ASD subjects, cytokine production by purified peripheral blood monocytes (PB Mo) and mitochondrial function measured as oxygen consumption rate (OCR) in peripheral blood mononuclear cells (PBMCs) were examined. A positive association between OCR and IL-1ß production was observed with TLR4 and TLR7/8 agonists in both ASD and controls. Because of variable responses to zymosan, a TLR2/6 agonist, ASD samples stimlated with zymosan were divided into three groups defined by the IL-1ß/IL-10 ratio results based on the reference values from 33 non-ASD controls. ASD cells with higher IL-1β/IL-10 ratio (N=15) showed no association between OCR and IL-1β production. Cells with lower IL-1β/IL-10 ratio (N=7) showed a negative association, while those with normal IL-1β/IL-10 ratios (N=49) revealed a positive association (r=-0.506 vs. 0.37, r=-0.466 vs. 0.344 for ATP linked and maximal OCR, respectively, for these 2 groups). Non-ATP linked OCR which is associated with oxygen burst revealed the similar tendency in these 2 groups (r=-0.455 vs. 0.385). ASD subjects with higher or lower IL-1β/IL-10 ratio with zymosan had chronic gastrointestinal (GI) symptoms. Our results indicates an association between IL-1ß production by innate immune cells and mitochondrial function of immune cells. Altered its association in some ASD subjects may be associated with their chronic GI symptoms.