1,25-Dihydroxyvitamin D3 Prevents Insulitis in NOD Mice

Abstract

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 micrograms/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 +/- 0.1 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.

Dendritic cell modulation by 1α,25 dihydroxyvitamin D3and its analogs: A vitamin D receptor-dependent pathway that promotes a persistent state of immaturityin vitroandin vivo

“…The influence of 1␣,25(OH) 2 D 3 on immune function has been the subject of numerous reports (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Direct modulation of T cells and macrophage͞monocytes by 1␣,25(OH) 2 D 3 has been documented in vitro (13)(14)(15).…”

Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice

“…Pancreases from all experimental groups at 100 and 250 days were embedded in optimal cutting temperature (OCT) medium, snap-frozen in 2-methyl-butane 99% + chilled in liquid nitrogen and stored at −80°C until processing [20]. 5-µm cryostat sections were stained with Mayer's haematoxylin and eosin.…”

Allelic variation in the vitamin D receptor influences susceptibility to IDDM in Indian Asians

“…The active form of vitamin D (1,25 dihydroxyvitamin D3) inhibits T cell proliferation and suppresses both tumour necrosis factor a (TNFa) and interleukin-1 production [24]. Furthermore, in the NOD mouse (an excellent animal model of IDDM) vitamin D3 administration prevents the development of IDDM as well as the associated autoimmune insulitis [25]. In a recent study in Bangladeshi subjects living in east London, vitamin D levels were found to be reduced in those most at risk for non-insulin-dependent diabetes [26].…”