Altered cytokine profiles and elevated lactate levels in children with autism spectrum disorder: indications of a dysregulated immune-metabolic network?

Abstract

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. Methods We measured blood lactate and pyruvate and quantified a cytokine/chemokine panel including IL-1β, IL-2, IL-6, TNF-α, IL-8, IFN-β, RANTES, MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/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. Results We observed elevated lactate levels, lower concentrations of IL-1β and TNF-α in autistic- compared with control children. In addition, lactate, MIP-1β/CCL4 and TNF-α was significantly associated with behavioral measures of autistic behavior. Pyruvate, the lactate/pyruvate ratio and all other analytes did not differ between groups. Discussion 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.