Prevention of autoimmune diabetes by oral administration of syngeneic pancreatic extract to young NOD mice

Oral administration of relevant autoantigens is being considered as a reali stic approach for the prevention of several autoimmune diseases. In this st udy we administered, orally, to young female NOD/Ak mice (diabetes incidenc e, 40%) and NOD/LtJ mice (diabetes incidence, 70%) whole pancreatic extract on days 19, 20, 21, 22, 23, 26, and 27 and studied its effects on the deve lopment of diabetes until day 250. The cumulative incidence of diabetes in both the colonies after pancreatic extract treatment was compared with the incidence after oral administration of syngeneic liver extract or in untrea ted mice. In the NOD/Ak mice, the incidence of diabetes in the pancreatic e xtract group was significantly lower (6%; n = 34, p = 0.004) and was delaye d compared with 33% In the liver group (n = 34) and 44% in the untreated gr oup (n = 18). Significant protection from diabetes and a delay in its onset also were observed in the NOD/LtJ mice treated with pancreatic extract (16 %; n = 19, p = 0.002) compared with those liver extract treated (72%; n = 1 8) and in untreated mice (60%; n = 22). Pancreatic histology at day 90 from all the study groups showed that the protection from diabetes in the pancr eatic-extract group was not associated with reduced insulitis. We speculate that the marked disease protection observed in this study with orally admi nistered pancreatic extract may be associated with the presence of immunore gulatory cells with a predominant Th2 cytokine bias. Our studies may have i mplications for the prevention of insulin-dependent diabetes mellitus (IDDM ) in humans.