Prevention of type 1 diabetes by inducing subclinical dermatitis on a small area

We have previously epidemiologically shown that type 1 diabetes is inversely associated with contact allergy. This finding is intriguing as type 1 diabetes and contact allergy are two completely different diseases, although T cells are involved in both diseases. The objective of this study was therefore to experimentally study the effect of contact allergens on the development of diabetes in non-obese diabetic mice.

Non-obese diabetic mice 4 weeks of age were separated into seven groups. One group was exposed to tapped water every 14th day, whereas the remaining six groups were split into sensitizations groups or elicitation groups (exposure every 14th day). These groups were then treated with one of the selected contact allergens (PPD or DNCB) or vehicle (AOO). All groups received the sensitizing treatment regime, and hereafter only the elicitation groups were further treated. If the blood glucose reached 14 mM, the mice were considered diabetic and euthanized. Cardiac heart blood was drawn at euthanization, and a Luminex analysis was done on the serum.

We showed that repeated application of a low dose of PPD reduced the incidence of diabetes compared to application with water (47% versus 93%, p=0.004). The rest of the groups developed diabetes with a cumulative incidence rate above 80%. The Luminex cytokine analysis revealed no differences between the groups, and no elevated cytokine level suggested a systemic response. Dermatitis was not noticeable by visual inspection, a histological examination, however, revealed a slight infiltration in the ears in the elicitation groups exposed to contact allergens.

This study showed that repeated topical application on the ears with a contact allergen could prevent the development of diabetes in non-obese diabetic mice. The contact allergens gave a non-visible, subclinical dermatitis on the application site. Activation of NKT cells to the ear lymph nodes seems to be involved.