Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors

Biochim Biophys Acta. 2012 Jun;1822(6):831-42. doi: 10.1016/j.bbadis.2012.01.011. Epub 2012 Feb 2.


Abnormal immune responses have been reported to be associated with autism. A number of studies showed that cytokines were increased in the blood, brain, and cerebrospinal fluid of autistic subjects. Elevated IL-6 in autistic brain has been a consistent finding. However, the mechanisms by which IL-6 may be involved in the pathogenesis of autism are not well understood. Here we show that mice with elevated IL-6 in the brain display many autistic features, including impaired cognitive abilities, deficits in learning, abnormal anxiety traits and habituations, as well as decreased social interactions. IL-6 elevation caused alterations in excitatory and inhibitory synaptic formations and disrupted the balance of excitatory/inhibitory synaptic transmissions. IL-6 elevation also resulted in an abnormal change in the shape, length and distributing pattern of dendritic spines. These findings suggest that IL-6 elevation in the brain could mediate autistic-like behaviors, possibly through the imbalances of neural circuitry and impairments of synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety
  • Autistic Disorder / genetics
  • Autistic Disorder / immunology*
  • Autistic Disorder / pathology
  • Brain / immunology*
  • Brain / metabolism
  • Brain / ultrastructure
  • Cognition
  • Dendritic Spines / immunology
  • Dendritic Spines / metabolism
  • Dendritic Spines / ultrastructure
  • Excitatory Postsynaptic Potentials
  • Genetic Vectors
  • Green Fluorescent Proteins / genetics
  • Inhibitory Postsynaptic Potentials
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Mice
  • Mice, Transgenic
  • Neuronal Plasticity
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Synaptic Transmission* / genetics
  • Synaptic Transmission* / immunology


  • Interleukin-6
  • Green Fluorescent Proteins