Elevated Cytokines in the Brain of Autistic Individuals

Background: Although the pathogenesis of autistic spectrum disorders (ASD) is not understood, recent studies have suggested that localized inflammation of the central nervous system may contribute to the pathogenesis of ASD. A number of studies have shown that TNFα, IFNγ, IL-1β and IL-12 were increased in the peripheral blood of ASD subjects.  However, it is difficult to interpret these findings with respect to the pathogenesis of ASD since it is not clear that the immune findings in peripheral blood mononuclear cells in autistic subjects correlate with immune-mediated pathology within the central nervous system. Recently, it has been reported that TNFα was increased in the cerebral spinal fluid of autistic patients. However, only one study has been conducted to investigate the inflammatory cytokine profile in the brain of autistic individuals using a cytokine protein array method (Vargas et al., 2005). 

Objectives: The aim of this study is to further investigate whether immune-mediated mechanisms are involved in the pathogenesis of autism and gain a clearer picture of cytokine activities in the brain of autistic individuals.

Methods: Invitrogen's Multiplex Bead Immunoassays (Human Cytokine 10-plex) were used to determine the levels of different cytokines in the cerebral front cortex from 8 autistic subjects and age-matched controls. Cytokine levels were measured with a Luminex 200^TM system (Bio-Rad Laboratories). Raw data (mean fluorescent intensities) were analyzed by Bio-Plex Manager Software 4.1 version (Bio-Rad Laboratories) to obtain concentration values.

Results: Our results showed that proinflammatory cytokines (TNF-α, IL-6 and GM-CSF), Th1 cytokine (IFN-γ) and chemokine (IL-8) were significantly increased in the brains of ASD subjects compared with the controls.  However the Th2 cytokines (IL-4, IL-5 and IL-10) showed no significant difference. The Th1/Th2 ratio was also significantly increased in ASD patients. 

Conclusions: ASD patients displayed an increased innate and adaptive immune response through the Th1 pathway, suggesting that localized brain inflammation and autoimmune disorder may be involved in the pathogenesis of ASD.