Abstract
Neonatal diet may influence the development of type 1 diabetes (T1D) in susceptible individuals through an intestinal mucosal inflammatory response, resulting in loss of self-tolerance. We tested the hypothesis that formula feeding during the neonatal period accelerates the development of T1D in diabetes-prone BioBreeding (BBDP) rats through regulation of CD4+CD25+ regulatory T lymphocytes (Treg) and anti-inflammatory cytokines. BBDP rat pups fed rat milk substitute (RMS) via a “pup-in-the cup” system were compared with mother-fed (MF) rats. The spleen and thymus were analyzed for Foxp3-expressing CD4+/CD25+ T cells. Multiplex enzyme-linked immunosorbent assays (ELISAs) were performed to measure cytokine-induced neutrophil chemoattractant (CINC), tumor necrosis factor α (TNF-α), interferon-gamma (IFN-γ), interleukin (IL)-4, IL-10, and IL-18. Diabetes-free survival, time of disease onset, and Treg/total T lymphocyte ratios were not different. MF pups had higher ileal CINC (p < 0.001) and IL-18 (p = 0.002), but no differences in the liver. There were no differences in ileal cytokine concentrations of 75-d-old rats, but the formula-fed rats had greater liver TNF-α (p < 0.001), IFN-γ, and IL-4 (p < 0.01) and lower IL-10 (p = 0.002) compared with MF animals. Formula versus maternal milk altered the hepatic cytokine profile at 75 d toward an inflammatory pattern but did not result in altered Treg cell frequencies or the development of T1D.
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Abbreviations
- BBDP:
-
diabetes-prone BioBreeding
- CINC:
-
cytokine-induced neutrophil chemoattractant
- RMS:
-
rat milk substitute
- T1D:
-
type 1 diabetes
- Treg:
-
CD4+CD25+ regulatory T lymphocytes
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Caicedo, R., Li, N., Robert, C. et al. Neonatal Formula Feeding Leads to Immunological Alterations in an Animal Model of Type 1 Diabetes. Pediatr Res 63, 303–307 (2008). https://doi.org/10.1203/PDR.0b013e31815ed662
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DOI: https://doi.org/10.1203/PDR.0b013e31815ed662
