Oral administration of insulin to neonates suppresses spontaneous and cyclophosphamide induced diabetes in the NOD mouse

Oral administration of autoantigens to adult mice is an effective means of suppressing experimental autoimmune diseases including diabetes and experim ental allergic encephalomyelitis (EAE). Different mechanisms are involved i n induction of oral tolerance including active suppression, anergy and dele tion. Oral tolerance is generally not inducible in the neonatal period and we previously found that EAE development in Lewis rats is enhanced when ani mals are fed myelin antigens as neonates. Here we report the unexpected fin ding that oral administration of either human insulin or the insulin B-chai n peptide (10-24) in the neonatal period suppresses the development of diab etes in the non-obese diabetic (NOD) mouse. Furthermore, suppression of dia betes by neonatal oral human insulin was more effective than oral human ins ulin given to NOD mice (3-4 weeks of age). No protection against EAE was ob served in NOD mice neonatally fed PLP (48-70) or MOG (35-55) peptide prior to EAE induction, whereas adult NOD mice orally tolerized to these peptides were protected against EAE. Neonatal administration of insulin B-chain pep tide also suppressed cyclophosphamide induced diabetes in the NOD whereas o ral insulin administration to 4-week-old NOD mice had no effect, suggesting that the mechanism of disease suppression in the neonate involved anergy o r deletion. Our findings that neonatal feeding of human insulin or insulin B-chain peptide is effective in inhibiting diabetes when given to the NOD m ouse may have applications in preventing diabetes in high risk human popula tions. (C) 2001 Academic Press.