Branisteanu D D, Waer M, Sobis H, Marcelis S, Vandeputte M, Bouillon R
Laboratory for Experimental Medicine and Endocrinology (LEGENDO), U.Z. Gasthuisberg, Katholieke Universiteit Leuven, Belgium.
J Neuroimmunol. 1995 Sep;61(2):151-60. doi: 10.1016/0165-5728(95)00076-e.
The hormone 1 alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3) has immune modulatory activities in vitro and in vivo, and can prevent or delay the onset of experimental or spontaneous autoimmune diseases. At therapeutical doses, however, hypercalcemic side effects are found. The present experiments examined the effects of combined treatment with subtherapeutic doses of cyclosporine A (CsA) and 1,25(OH)2D3 on the evolution of experimental autoimmune encephalomyelitis (EAE) in SJL mice. 1,25(OH)2D3 at 5 micrograms/kg body weight (given by i.p. injection every 2 days) prevented the appearance of paralysis in 70% of the treated mice. The treatment with 1,25(OH)2D3 at 2 micrograms/kg/2 days alone had less substantial protective effects (22% disease-free animals versus 5% in the control group). However, when this subtherapeutic dose was associated to treatment with a daily dose of CsA (2 or 5 mg/kg/day), which by itself was subtherapeutic (24 and 50% disease-free animals, respectively), the association of both drugs led to near-total protection (86% disease-free animals when combined with the highest dose of CsA). When an alternate day administration schedule (CsA at 10 mg/kg and 1,25(OH)2D3 at 2 micrograms/kg, each given on alternate days from day -3 to +19 after disease induction) was used, all treated mice were completely protected clinically and histologically. The two drugs also showed additive effects on serum osteocalcin and urinary calcium and desoxypyridinoline excretion, but not on serum calcium concentration. Our experiments demonstrate that 1,25(OH)2D3 might be a potential dose-reducing agent for CsA in immunosuppressive therapy.
激素1α,25 - 二羟基维生素D3（1,25(OH)2D3）在体外和体内均具有免疫调节活性，并且能够预防或延缓实验性或自发性自身免疫性疾病的发生。然而，在治疗剂量下会出现高钙血症副作用。本实验研究了亚治疗剂量的环孢素A（CsA）与1,25(OH)2D3联合治疗对SJL小鼠实验性自身免疫性脑脊髓炎（EAE）病程的影响。体重5微克/千克的1,25(OH)2D3（每2天腹腔注射一次）可使70%接受治疗的小鼠避免出现麻痹症状。单独使用2微克/千克/2天的1,25(OH)2D3治疗的保护作用较弱（无疾病动物为22%，而对照组为5%）。然而，当该亚治疗剂量与每日剂量的CsA（2或5毫克/千克/天）联合使用时（CsA单独使用时亚治疗效果分别为24%和50%无疾病动物），两种药物联合使用可实现近乎完全的保护（与最高剂量的CsA联合使用时，86%无疾病动物）。当采用隔日给药方案（疾病诱导后第 -3天至 +19天，CsA 10毫克/千克和1,25(OH)2D3 2微克/千克隔日给药）时，所有接受治疗的小鼠在临床和组织学上均得到完全保护。这两种药物对血清骨钙素、尿钙和脱氧吡啶啉排泄也显示出相加作用，但对血清钙浓度无影响。我们的实验表明，在免疫抑制治疗中，1,25(OH)2D3可能是一种降低CsA剂量的潜在药物。
