Associations between cytokines, endocrine stress response, and gastrointestinal symptoms in autism spectrum disorder

Brain Behav Immun. 2016 Nov;58:57-62. doi: 10.1016/j.bbi.2016.05.009. Epub 2016 May 12.


Many children and adolescents with autism spectrum disorder (ASD) have significant gastrointestinal (GI) symptoms, but the etiology is currently unknown. Some individuals with ASD show altered reactivity to stress and altered immune markers relative to typically-developing individuals, particularly stress-responsive cytokines including tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Acute and chronic stress is associated with the onset and exacerbation of GI symptoms in those without ASD. The present study examined whether GI symptoms in ASD were associated with increases in cortisol, a stress-associated endocrine marker, and TNF-α and IL-6 in response to stress. As hypothesized, a greater amount of lower GI tract symptoms were significantly associated with post-stress cortisol concentration. The relationship between cortisol response to stress and GI functioning was greater for children who had a history of regressive autism. Exploratory analyses revealed significant correlations between cortisol response, intelligence, and inappropriate speech. In contrast, symptoms of the lower GI tract were not associated with levels of TNF-α or IL-6. Significant correlations were found, however, between TNF-α and IL-6 and irritability, socialization, and intelligence. These findings suggest that individuals with ASD and symptoms of the lower GI tract may have an increased response to stress, but this effect is not associated with concomitant changes in TNF-α and IL-6. The relationship between cortisol stress response and lower GI tract symptoms in children with regressive autism, as well as the relationships between cortisol, IL-6, and intelligence in ASD, warrant further investigation.

Keywords: Autism spectrum disorder; Cortisol; Cytokines; Gastrointestinal disorders; Stress.

MeSH terms

  • Adolescent
  • Autism Spectrum Disorder / complications*
  • Autism Spectrum Disorder / immunology*
  • Child
  • Cytokines / metabolism
  • Endocrine System / immunology
  • Female
  • Gastrointestinal Diseases / complications*
  • Gastrointestinal Diseases / immunology*
  • Humans
  • Hydrocortisone / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Stress, Psychological / complications*
  • Stress, Psychological / immunology*
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • IL6 protein, human
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Hydrocortisone