Evaluation of Cytokine Expression In Cerebral Cortex and Blood Plasma of Autistic Patients

Background: Autism is an idiopathic pervasive neurodevelopmental disorder associated with an atypical immunological response evidenced by an altered systemic immunological profile and a neuroinflammatory process in the CNS of autistic individuals.  Cytokines are involved in the regulation of inflammatory responses, and increased levels of subsets of cytokines have been demonstrated in the PBMC, sera, CSF, brain tissue and intracellularly in ASD patients.  Genotypic analysis of polymorphic sites in some cytokine genes of autistic individuals has yielded significant results, but the picture is still incomplete. Cytokine expression analyses in autism should provide a better understanding of the potential role of the immune system in this disease.

Objectives: The current study has two main objectives. The first objective is to perform transcriptional profiling of a panel of cytokine and chemokine genes in different regions of post-mortem brain tissues of autistic subjects and controls.  The second objective is to perform translational profiling of a panel of cytokine and chemokine genes in the blood plasma of autistic subjects.  

Methods: Post-mortem brain tissue samples were provided by the Autism Tissue Program. After RNA extraction, transcriptional profiling was performed by reverse transcription - real time PCR in 5 cortical regions: BA 4, 9, 17, 22 and 46.  Blood plasma samples were provided by the Kosair Children’s Hospital Pediatric Clinical Research Unit.  Protein expression analysis was performed using LUMINEX technology.

Results: Preliminary transcriptional analysis revealed that cytokine (TNFα, IL-6, TGFβ1, IL-1β), and chemokine (IL-8) transcripts were increased in all brain regions (especially BA 46, dorsolateral prefrontal cortex) except BA 22 (superior temporal gyrus/Wernicke’s area) in autism as compared with controls. Preliminary plasma analysis revealed an altered expression of cytokine and chemokine regulation systemically in autistic patients when compared to literature values for controls.

Conclusions: This study reveals an up-regulation of cytokine and chemokine expression in autism in various cortical regions and an altered expression of these proteins systemically. The current data suggest a heterogeneous regulation of cytokine gene transcription in the cerebral cortex of autistic patients, where different brain regions show a differential cytokine transcription profile. Additionally, this data suggests an atypical expression of cytokines in blood plasma of autistic individuals.