Research Article: Altered cytokine profiles and elevated lactate levels in children with autism spectrum disorder: indications of a dysregulated immune-metabolic network?
Abstract:
Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition characterized by difficulties in social communication and restricted, repetitive behavior. The etiology and pathophysiology of ASD remain largely unknown; however, a complex interplay of genetic and environmental factors is widely assumed. More recently, altered cytokine/chemokine profiles and a potential vulnerability to mitochondrial alterations have been proposed.
We measured blood lactate and pyruvate and quantified a cytokine/chemokine panel including IL-1?, IL-2, IL-6, TNF-?, IL-8, IFN-?, RANTES, MCP-1/CCL2, MIP-1?/CCL3, MIP-1?/CCL4, CCL11/Eotaxin-1 and CXCL10/IP-10 in a group of autistic children in comparison to a non-autistic age-, gender- and IQ-matched control group.
We observed elevated lactate levels, lower concentrations of IL-1? and TNF-? in autistic- compared with control children. In addition, lactate, MIP-1?/CCL4 and TNF-? was significantly associated with behavioral measures of autistic behavior. Pyruvate, the lactate/pyruvate ratio and all other analytes did not differ between groups.
We conclude that the observed cytokine/chemokine profile may reflect a dysregulated immunological network in autistic children. Elevated lactate may point to metabolic abnormalities with possible mitochondrial involvement. However, unchanged pyruvate and lactate/pyruvate ratio do not support overt mitochondrial dysfunction. These findings require replication in larger studies.
Introduction:
Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition characterized by difficulties in social communication and restricted, repetitive behavior. The etiology and pathophysiology of ASD remain largely unknown; however, a complex interplay of genetic and environmental factors is widely assumed. More recently, altered cytokine/chemokine profiles and a potential vulnerability to mitochondrial alterations have been proposed.
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