Cytokine profiles by peripheral blood monocytes are associated with changes in behavioral symptoms following immune insults in a subset of ASD subjects: An inflammatory subtype?

Background: some children with autism spectrum disorders (asd) are characterized by fluctuating behavioral symptoms following immune insults,persistent gastrointestinal (gi) symptoms,and a lack of response to the first-line intervention measures. these children have been categorized as the asd-inflammatory subtype (asd-is) for this study. we reported a high prevalence of non-ige mediated food allergy (nfa) in young asd children before,but not all asd/nfa children reveal such clinical features of asd-is. this study addressed whether behavioral changes of asd-is are associated with innate immune abnormalities manifested in isolated peripheral blood (pb) monocytes (mo),major innate immune cells in the pb. methods: this study includes three groups of asd subjects (asd-is subjects (n = 24),asd controls with a history of nfa (asd/nfa (n = 20),and asd/non-nfa controls (n = 20)) and three groups of non-asd controls (non-asd/nfa subjects (n = 16),those diagnosed with pediatric acute onset-neuropsychiatric syndrome (pans,n = 18),and normal controls without nfa or pans (n = 16)). functions of purified pb mo were assessed by measuring the production of inflammatory and counter-regulatory cytokines with or without stimuli of innate immunity (lipopolysaccharide (lps),zymosan,cl097,and candida heat extracts as a source of β-lactam). in asd-is and pans subjects,these assays were done in the state of behavioral exacerbation ('flare') and in the stable ('non-flare') condition. asd-is children in the 'flare' state revealed worsening irritability,lethargy and hyperactivity. results: 'flare' asd-is pb mo produced higher amounts of inflammatory cytokines (il-1β and il-6) without stimuli than 'non-flare' asd-is cells. with zymosan,'flare' asd-is cells produced more il-1β than most control cells,despite spontaneous production of large amounts of il-1β. moreover,'flare' asd-is mo produced less il-10,a counterregulatory cytokine,in response to stimuli than 'non-flare' cells or other control cells. these changes were not observed in pans cells. conclusions: we observed an imbalance in the production of inflammatory (il-1β and il-6) and counterregulatory (il-10) cytokines by 'flare' asd-is monocytes,which may indicate an association between intrinsic abnormalities of pb mo and changes in behavioral symptoms in the asd-is subjects. © 2014 jyonouchi et al.