A wheat-based, diabetes-promoting diet induces a Th1-type cytokine bias in the gut of NOD mice

Cytokine. 2003 Feb 7;21(3):149-54. doi: 10.1016/s1043-4666(02)00486-6.


Dietary antigens are candidate environmental factors in the pathogenesis of type 1 diabetes. In the non-obese diabetic (NOD) mouse, an animal model of type 1 diabetes, cereal-based diets promote disease development, whereas the diets based on hydrolysed proteins or non-diabetogenic proteins are protective. The hypothesis that diabetogenic diets modulate the cytokine balance in the gut was tested. NOD mice were fed with NTP-2000 (mainly a wheat-based milk-free diet) or Prosobee (a semi-purified hypoallergenic diet based on soy protein isolate) or Prosobee plus casein (milk protein fraction). The mRNA levels of IFN-gamma, IL-10, TNF-alpha, TGF-beta, and inducible NO synthase in the small intestine and the Peyer's patches were determined by semi-quantitative RT-PCR. Mice fed on the cereal-based NTP-2000 diet expressed higher levels of the Th1-type and pro-inflammatory markers IFN-gamma, TNF-alpha, and inducible NO synthase mRNA compared to the Prosobee-fed animals. The expression of the counterregulatory cytokines IL-10 and TGF-beta was unaffected. This resulted in a significant bias of the intestinal cytokine balance towards T helper cell type 1 after feeding NTP-2000. The cytokine mRNA levels in the gut-associated Peyer's patches were not affected. Thus, modulation of gut immunoreactivity by diet may contribute to disease development in NOD mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Feed*
  • Animals
  • Caseins / pharmacology
  • Cytokines / metabolism
  • DNA, Complementary / metabolism
  • Diabetes Mellitus / chemically induced*
  • Diet, Diabetic*
  • Edible Grain
  • Female
  • Gastrointestinal Tract / metabolism*
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / biosynthesis
  • Mice
  • Mice, Inbred NOD
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase Type II
  • Peyer's Patches
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Th1 Cells / metabolism*
  • Transforming Growth Factor beta / biosynthesis
  • Triticum*
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Caseins
  • Cytokines
  • DNA, Complementary
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse