Rizka Aulia, Setiati Siti, Harimurti Kuntjoro, Sadikin M, Mansur Indra G
1. Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo Hospital, Jakarta, Indonesia 2. Metabolic Vascular and Aging Cluster, Indonesian Medical Education and Research Institute, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.
Acta Med Indones. 2018 Jul;50(3):215-221.
Alphacalcidol, a vitamin D analog, shows immune regulatory potency as it works on the macrophage and T cell to control inflammation and T cell dysregulation in elderly. None has been known about its effect on elderly with various states of frailty syndrome, which have different level of chronic low grade inflammation. This study aimed to determine the effect of alphacalcidol on inflammatory cytokines (IL-6, IL-10, g-IFN ) and T cell subsets (CD4/CD8 ratio and CD8+ CD28-) of elderly with various stages of frailty syndrome.
from January to July 2017, a double blind randomized controlled trial (RCT) with allocation concealment, involving 110 elderly subjects from Geriatric Outpatient Clinic Cipto Mangunkusumo Hospital Jakarta, was conducted to measure the effect of 0.5 mcg alphacalcidol administration for 90 days to inflammatory cytokines (IL-6, IL-10, g-IFN) from PBMC culture supernatant, as well as CD4/CD8 and CD8+CD28- percentage using flow cytometry. Statistical analysis using SPSS version 20 was performed with t-test to measure mean difference.
of 110 subjects involved in the RCT consisting of 27 fit, 27 pre-frail and 56 frail elderly, 25(OH)D serum level was found to be as low as 25.59 (12.2) ng/ml in alphacalcidol group and 28.27 (10.4) ng/ml in placebo group. Alphacalcidol did not decrease IL-6 (p=0.4) and g- IFN (p=0.001), but it increased IL-10 (p=0,005) and decreased IL6/IL10 ratio (p=0.008). Alphacalcidol increased CD4/CD8 ratio from 2.68 (SD 2.45) to 3.2 (SD 2.9); p=0.001 and decreased CD8+ CD28- percentage from 5.1 (SD 3.96) to 2.5 (1.5); p<0.001. Sub group analysis showed similar patterns in all frailty states.
Alphacalcidol improves immune senescence by acting as anti-inflammatory agent through increased IL-10 and decreased IL6/IL-10 ratio and also improves cellular immunity through increased CD4/CD8 ratio and decreased CD8+ CD28- subset in elderly. This effect is not influenced by frailty state.
阿法骨化醇是一种维生素D类似物，对巨噬细胞和T细胞发挥作用，从而控制老年人的炎症反应和T细胞失调，显示出免疫调节效能。目前尚不清楚其对患有不同程度慢性低度炎症的各种衰弱综合征状态的老年人的影响。本研究旨在确定阿法骨化醇对处于不同衰弱综合征阶段的老年人炎症细胞因子（白细胞介素-6、白细胞介素-10、γ-干扰素）和T细胞亚群（CD4/CD8比值和CD8+CD28-）的影响。
2017年1月至7月，在雅加达芝多马古苏莫医院老年门诊进行了一项采用分配隐藏的双盲随机对照试验（RCT），纳入110名老年受试者，以测量给予0.5微克阿法骨化醇90天对来自外周血单个核细胞（PBMC）培养上清液中的炎症细胞因子（白细胞介素-6、白细胞介素-10、γ-干扰素）以及采用流式细胞术检测CD4/CD8和CD8+CD28-百分比的影响。使用SPSS 20版进行统计分析，采用t检验来测量均值差异。
在参与RCT的110名受试者中，包括27名健康老人、27名衰弱前期老人和56名衰弱老人，阿法骨化醇组血清25(OH)D水平低至25.59（12.2）纳克/毫升，安慰剂组为28.27（10.4）纳克/毫升。阿法骨化醇未降低白细胞介素-6（p=0.4）和γ-干扰素（p=0.001），但升高了白细胞介素-10（p=0.005）并降低了白细胞介素6/白细胞介素10比值（p=0.008）。阿法骨化醇使CD4/CD8比值从2.68（标准差2.45）升高至3.2（标准差2.9）；p=0.001，并使CD8+CD28-百分比从5.1（标准差3.96）降至2.5（1.5）；p<0.001。亚组分析显示在所有衰弱状态下均有类似模式。
阿法骨化醇通过增加白细胞介素-10和降低白细胞介素6/白细胞介素-10比值，作为抗炎剂发挥作用，改善免疫衰老，并且通过升高CD4/CD8比值和降低CD8+CD28-亚群来改善老年人的细胞免疫。这种作用不受衰弱状态的影响。
