Larsson P, Mattsson L, Klareskog L, Johnsson C
Department of Rheumatology, Karolinska Hospital, Stockholm, Sweden.
Clin Exp Immunol. 1998 Nov;114(2):277-83. doi: 10.1046/j.1365-2249.1998.00706.x.
The immunomodulatory properties of the vitamin D analogue MC 1288 (20-epi-1alpha,25-dihydroxycholecalciferol) were investigated in CIA in rats. The analogue was administered systemically at three different time points; (i) for 10 consecutive days before collagen (CII) immunization; (ii) for 10 consecutive days after CII immunization; or (iii) for 7 consecutive days from disease onset. Treatment initiated either 10 days before CII immunization or at the day of collagen immunization effectively suppressed the development of arthritis. Treatment initiated at the day of the onset of arthritis reduced the severity of joint inflammation. Significantly, doses which did not induce hypercalcaemia decreased the incidence and severity of arthritis. In vivo treatment with the 20-epi analogue of 1alpha,25-dihydroxycholecalciferol diminished the serum levels of antibodies to rat CII. Similarly, mitogen-induced proliferation of lymph node cells from rat CII-immunized animals was reduced. The experiments demonstrate that the vitamin D analogue MC 1288 has the ability to prevent, and furthermore to suppress, already established CIA by its immunomodulatory properties without inducing hypercalcaemia.
在大鼠胶原诱导性关节炎（CIA）模型中研究了维生素D类似物MC 1288（20-表-1α,25-二羟基胆钙化醇）的免疫调节特性。该类似物在三个不同时间点进行全身给药：（i）在胶原蛋白（CII）免疫前连续给药10天；（ii）在CII免疫后连续给药10天；或（iii）从疾病发作开始连续给药7天。在CII免疫前10天或胶原蛋白免疫当天开始治疗可有效抑制关节炎的发展。在关节炎发作当天开始治疗可减轻关节炎症的严重程度。值得注意的是，不引起高钙血症的剂量可降低关节炎的发病率和严重程度。用1α,25-二羟基胆钙化醇的20-表类似物进行体内治疗可降低大鼠抗CII抗体的血清水平。同样，丝裂原诱导的来自大鼠CII免疫动物的淋巴结细胞增殖也减少。实验表明，维生素D类似物MC 1288具有通过其免疫调节特性预防并进一步抑制已建立的CIA的能力，且不会引起高钙血症。
