A wheat-based, diabetes-promoting diet induces a Th1-type cytokine bias in the gut of NOD mice.
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.
Flohé
S B
SB
German Diabetes Research Institute, Auf'm Hennekamp 65, Düsseldorf 40225, Germany.
Wasmuth
H E
HE
Kerad
J B
JB
Beales
P E
PE
Pozzilli
P
P
Elliott
R B
RB
Hill
J P
JP
Scott
F W
FW
Kolb
H
H
D000821:Animal Feed; D000818:Animals; D002364:Caseins / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D003920:Diabetes Mellitus / Q000139:chemically induced*; D003927:Diet, Diabetic; D002523:Edible Grain; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D051379:Mice; D016688:Mice, Inbred NOD; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D010581:Peyer's Patches; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014908:Triticum; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D002364:Caseins; D016207:Cytokines; D018076:DNA, Complementary; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse