1,25-Dihydroxyvitamin D₃ Prevents Insulitis in NOD Mice

The active form of vitamin D, 1,25(OH)₂D₃, can prevent various forms of experimentally induced autoimmune disorders. The aim of this study was to confirm these findings in NOD mice that spontaneously develop an autoimmune type of diabetes mellitus. Therefore, the effect of a long-term 1,25(OH)₂D₃ treatment on the incidence of insulitis, the histological lesion preceding diabetes, was studied. Forty-three NOD mice were treated with 1,25(OH)₂D₃ (5 μg/kg) i.p. every other day from age 21 days on, when no insulitis was present yet. At day 100,16 control mice receiving the treatment vehicle (arachis oil) had an incidence of insulitis of 75%, whereas only 41% of the 1,25(OH)₂D₃-treated animals developed insulitis (P < 0.025). Calcemia, determined 24 h after the last 1,25(OH)₂D₃ injection was 2.5 ± 0.3 mM, which was higher than in control animals (2.3 ± 0.1 mM), but was well tolerated. Cellular immunity, as assessed with the mixed lymphocyte reaction performed at day 100, was not impaired significantly. This study demonstrates that long-term treatment with high doses of 1,25(OH)²D₃ is able to decrease the incidence of insulitis in spontaneous autoimmune diabetes without major side effects.