Systemic maternal inflammation promotes ASD via IL-6 and IFN-γ.
Daniel MajerczykElizabeth G AyadKari L BrewtonPichrasmei SaingPeter C HartPublished in: Bioscience reports (2022)
Autism spectrum disorder (ASD) is a neurological disorder that manifests during early development, impacting individuals through their ways of communicating, social behaviors, and their ability to perform day-to-day activities. There have been different proposed mechanisms on how ASD precipitates within a patient, one of which being the impact cytokines have on fetal development once a mother's immune system has been activated (referred to as maternal immune activation, MIA). The occurrence of ASD has long been associated with elevated levels of several cytokines, including interleukin-6 (IL-6) and interferon gamma (IFN-γ). These proinflammatory cytokines can achieve high systemic levels in response to immune activating pathogens from various extrinsic sources. Transfer of cytokines such as IL-6 across the placental barrier allows accumulation in the fetus, potentially inducing neuroinflammation and consequently altering neurodevelopmental processes. Individuals who have been later diagnosed with ASD have been observed to have elevated levels of IL-6 and other proinflammatory cytokines during gestation. Moreover, the outcome of MIA has been associated with neurological effects such as impaired social interaction and an increase in repetitive behavior in animal models, supporting a mechanistic link between gestational inflammation and development of ASD-like characteristics. The present review attempts to provide a concise overview of the available preclinical and clinical data that suggest cross-talk between IL-6 and IFN-γ through both extrinsic and intrinsic factors as a central mechanism of MIA that may promote the development of ASD.
Keyphrases
- autism spectrum disorder
- attention deficit hyperactivity disorder
- intellectual disability
- dendritic cells
- oxidative stress
- immune response
- healthcare
- mental health
- risk assessment
- pregnant women
- stem cells
- birth weight
- traumatic brain injury
- pregnancy outcomes
- preterm infants
- cognitive impairment
- drinking water
- weight gain
- case report
- bone marrow
- body mass index
- brain injury
- subarachnoid hemorrhage
- physical activity
- cerebral ischemia
- multidrug resistant
- lps induced
- drug induced