Prevention of Diabetes in NOD Mice by Repeated Exposures to a Contact Allergen Inducing a Sub-Clinical Dermatitis

Abstract

BackgroundType 1 diabetes is an autoimmune disease, while allergic contact dermatitis although immune mediated, is considered an exposure driven disease that develops due to epicutanous contact with reactive low-molecular chemicals. The objective of the present study was to experimentally study the effect of contact allergens on the development of diabetes in NOD mice. As the link between contact allergy and diabetes is yet unexplained we also examined the effect of provocation with allergens on Natural Killer T (NKT) cells, since involvement of NKT cells could suggest an innate connection between the two diseases.MethodNOD mice 4 weeks of age were exposed, on the ears, to two allergens, p-phenylenediamine and 2,4-dinitrochlorobenzene respectively, to investigate the diabetes development. The mice were followed for a maximum of 32 weeks, and they were either repeatedly exposed to the allergens or only sensitized a week after arrival. The stimulation of NKT cells by the two allergens were additionally studied in C57BL/6 mice. The mice were sensitized and two weeks later provocated with the allergens. The mice were subsequently euthanized at different time points after the provocation.ResultsIt was found that repeated application of p-phenylenediamine reduced the incidence of diabetes compared to application with water (47% vs. 93%, P = 0.004). Moreover it was shown that in C57BL/6 mice both allergens resulted in a slight increment in the quantity of NKT cells in the liver. Application of the allergens at the same time resulted in an increased number of NKT cells in the draining auricular lymph node, and the increase appeared to be somewhat allergen specific as the accumulation was stronger for p-phenylenediamine.ConclusionThe study showed that repeated topical application on the ears with a contact allergen could prevent the development of diabetes in NOD mice. The contact allergens gave a non-visible, sub-clinical dermatitis on the application site.The preventive effect on diabetes may be due to stimulation of peripheral NKT cells, as shown for provocation with p-phenylenediamine in the C57BL/6 mouse. This epicutanous procedure may lead to new strategies in prevention of type 1 diabetes in humans.

Inverse Association between Rheumatoid Arthritis and Contact Allergy

“…The opposing theory is that CA modulates the immune system and lowers the risk of RA. Mortz et al (9) showed that CA is already prevalent in children and adolescents, and, furthermore, we have shown that CA can prevent the development of diabetes in the non-obese diabetic mouse, which is prone to develop diabetes type 1 (10).…”

Type-specific human papillomavirus detection in cervical smears in Romania

“…Treatment with probiotics has been suggested, but no final human results exist so far (104). Allergen induction of a minor eczema, which seems to facilitate proliferation of NKT cells, reduces diabetes incidence in NOD mice, which is likely to reflect the decreased risk of T1D in humans with allergic dermatitis (105). Treatment with α-GalCer might be considered, but caution regarding the effect on other organ systems may be the reason for the lack of human trials.…”

Keratin 8 modulates β-cell stress responses and normoglycaemia

“…Blood glucose monitoring for low-dose STZ experiments were performed daily between day 7-14 and thereafter once a week. Animals were considered diabetic when two consecutive measurements exceeded 14 mmol/l (Engkilde et al, 2010) Animals were killed and samples collected 48 hours after high-dose STZ treatment and 15 or 35 days after low-dose STZ.…”