Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease

Sci Adv. 2019 Aug 7;5(8):eaaw7756. doi: 10.1126/sciadv.aaw7756. eCollection 2019 Aug.


Celiac disease (CeD), caused by immune reactions to cereal gluten, is treated with gluten -elimination diets. Within hours of gluten exposure, either perorally or extraorally by intradermal injection, treated patients experience gastrointestinal symptoms. To test whether gluten exposure leads to systemic cytokine production time -related to symptoms, series of multiplex cytokine measurements were obtained in CeD patients after gluten challenge. Peptide injection elevated at least 15 plasma cytokines, with IL-2, IL-8, and IL-10 being most prominent (fold-change increase at 4 hours of 272, 11, and 1.2, respectively). IL-2 and IL-8 were the only cytokines elevated at 2 hours, preceding onset of symptoms. After gluten ingestion, IL-2 was the earliest and most prominent cytokine (15-fold change at 4 hours). Supported by studies of patient-derived gluten-specific T cell clones and primary lymphocytes, our observations indicate that gluten-specific CD4+ T cells are rapidly reactivated by antigen -exposure likely causing CeD-associated gastrointestinal symptoms.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / classification
  • CD4-Positive T-Lymphocytes / metabolism
  • Celiac Disease / immunology
  • Celiac Disease / metabolism
  • Celiac Disease / pathology*
  • Cytokines / blood*
  • Double-Blind Method
  • Female
  • Genotype
  • Glutens / administration & dosage*
  • Glutens / adverse effects
  • HLA Antigens / genetics
  • Humans
  • Interleukin-10 / blood
  • Interleukin-2 / blood
  • Interleukin-8 / blood
  • Male
  • Middle Aged
  • Placebo Effect
  • Vomiting / etiology
  • Young Adult


  • Cytokines
  • HLA Antigens
  • Interleukin-2
  • Interleukin-8
  • Interleukin-10
  • Glutens