Enhancement of 1,25-dihydroxyvitamin D3-mediated suppression of experimental autoimmune encephalomyelitis by calcitonin
Enhancement of 1,25-dihydroxyvitamin D3-mediated suppression of experimental autoimmune encephalomyelitis by calcitonin
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DOI：
10.1073/pnas.0813312106
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发表时间：
2009-03-31
影响因子：
11.1
通讯作者：
DeLuca, Hector F.
中科院分区：
文献类型：
--
作者：
Becklund, Bryan R.;Hansen, Donald W., Jr.;DeLuca, Hector F.
维生素D的活性形式1 α，25-二羟基维生素D-3 [1，25（OH）（2）D-3]可抑制多发性硬化症（MS）的实验性自身免疫性脑脊髓炎（EAE）模型中的疾病发展。然而，完全的疾病预防仅在显著提高血清钙水平的剂量下发生，因此限制了1，25（OH）（2）D-3作为潜在MS治疗剂的有用性。由于降钙素（CT）被认为是由高钙血症释放的，并已被证明具有抗炎作用，我们研究了1，25（OH）（2）D-3对EAE的抑制是否部分或全部由CT介导。连续给予药理剂量的CT并不能预防EAE。然而，CT和亚治疗剂量的1，25（OH）（2）D-3的组合可叠加抑制EAE，而不引起高钙血症。此外，CT降低了抑制疾病所需的1，25（OH）2D 3的剂量。我们的研究结果表明，CT可能是一个重要的因素，但不能完全解释1，25（OH）（2）D-3介导的EAE抑制。
The active form of vitamin D, 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3], suppresses disease development in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). However, complete disease prevention only occurs with doses that dramatically elevate serum calcium levels, thus limiting the usefulness of 1,25(OH)(2)D-3 as a potential MS therapeutic agent. Because calcitonin (CT) is believed to be released by hypercalcemia and has been shown to be anti-inflammatory, we examined whether suppression of EAE by 1,25(OH)(2)D-3 could be mediated either in part or entirely by CT. Continuous administration of pharmacological doses of CT did not prevent EAE. However, a combination of CT and a subtherapeutic dose of 1,25(OH)(2)D-3 additively suppressed EAE without causing hypercalcemia. Moreover, CT decreased the dose of 1,25(OH)2D3 required for disease suppression. Our results suggest that CT may be a significant factor but cannot account entirely for 1,25(OH)(2)D-3-mediated suppression of EAE.