Gastro-Immuno Research Laboratory (GIRL), Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus, Denmark,
Inflammopharmacology. 2014 Apr;22(2):95-103. doi: 10.1007/s10787-013-0197-1. Epub 2013 Dec 29.
Low serum vitamin D levels may provoke or aggravate Crohn's disease (CrD). Vitamin D3 is a well-known immune modulator that affects immune functions in vitro and may prevent CrD flares. Dendritic cells (DC) are key mediators of vitamin D3 effects. In this study, we describe changes in monocyte-derived DC (mo-DC) maturation marker expression and cytokine production following 26 weeks of oral vitamin D3 supplementation in CrD patients.
Ten CrD patients who had increased serum 25-hydroxy vitamin D levels after oral vitamin D3 and calcium treatment and ten seasonally matched placebo-treated patients were selected for this study. Mo-DC were generated before and after the 26 weeks and induced to mature upon lipopolysaccharide (LPS) stimulation. Maturation marker expression and cytokine production were analysed. Mo-DC function was analysed in a mixed leucocyte reaction (MLR).
Compared with baseline values, LPS-matured mo-DC exhibited reduced expression of CD80 and reduced production of the cytokines IL-10, IL-1β, and IL-6 following 26 weeks of oral vitamin D3 supplementation. Mo-DC performance in an allogeneic MLR was unchanged after vitamin D3 supplementation. Treatment with the placebo did not affect maturation markers, cytokine production, or the MLR.
Vitamin D3 treatment in CrD patients led to hypo-responsive LPS-stimulated mo-DC. This finding indicates that vitamin D3 levels have an impact on the monocytic precursors of mo-DC in vivo and may explain the positive effects of vitamin D3 supplementation on CrD patients. Alternatively, CrD patients with high serum vitamin D3 levels may represent a subgroup with low disease activity.
低血清维生素 D 水平可能引发或加重克罗恩病（CrD）。维生素 D3 是一种众所周知的免疫调节剂，可影响体外免疫功能，并可能预防 CrD 发作。树突状细胞（DC）是维生素 D3 作用的主要介质。在这项研究中，我们描述了 26 周口服维生素 D3 补充治疗后 CrD 患者单核细胞衍生的 DC（mo-DC）成熟标志物表达和细胞因子产生的变化。
选择了 10 例经口服维生素 D3 和钙治疗后血清 25-羟维生素 D 水平升高的 CrD 患者和 10 例季节性匹配的安慰剂治疗患者进行这项研究。在 26 周前后生成 mo-DC，并在脂多糖（LPS）刺激下诱导成熟。分析成熟标志物表达和细胞因子产生。在混合白细胞反应（MLR）中分析 mo-DC 功能。
与基线值相比，口服维生素 D3 补充 26 周后，LPS 成熟的 mo-DC 表现出 CD80 表达降低和 IL-10、IL-1β 和 IL-6 细胞因子产生减少。口服维生素 D3 补充后，mo-DC 在同种异体 MLR 中的性能没有变化。安慰剂治疗不会影响成熟标志物、细胞因子产生或 MLR。
CrD 患者的维生素 D3 治疗导致 LPS 刺激的 mo-DC 反应性降低。这一发现表明，维生素 D3 水平对体内 mo-DC 的单核前体细胞有影响，并可能解释维生素 D3 补充对 CrD 患者的积极影响。或者，血清维生素 D3 水平高的 CrD 患者可能代表疾病活动度低的亚组。
