Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Department of Rheumatology, Haukeland University Hospital, Bergen, Norway.
Clin Exp Immunol. 2014 Jun;176(3):452-60. doi: 10.1111/cei.12288.
The risk of osteoporosis increases in inflammatory disorders. In cell-mediated immune activation, interferon (IFN)-γ stimulates macrophage release of neopterin and increases the activity of indoleamine 2,3-dioxygenase (IDO), thereby stimulating tryptophan degradation along the kynurenine pathway. Plasma levels of neopterin and the kynurenine/tryptophan ratio (KTR) are thus markers of IFN-γ-mediated inflammation. Several kynurenine pathway metabolites (kynurenines) possess immunomodulatory properties. The aim of this study was to investigate associations between markers of IFN-γ-mediated inflammation and kynurenines with bone mineral density (BMD). The community-based Hordaland Health Study (HUSK), with middle-aged (46-49 years) and older (71-74 years) participants, was conducted from 1998 to 2000 (n = 5312). Hip BMD in relation to neopterin, KTR and kynurenines were investigated, using linear and logistic regression analyses. In the oldest group, neopterin (P ≤ 0·019) and KTR (P ≤ 0·001) were associated inversely with BMD after multiple adjustment. Comparing the highest to the lowest quartiles, the odds ratios of low BMD (being in the lowest quintile of BMD) in the oldest cohort were for neopterin 2·01 among men and 2·34 among women (P ≤ 0·007) and for KTR 1·80 for men and 2·04 for women (P ≤ 0·022). Xanthurenic acid was associated positively with BMD in all sex and age groups while 3-hydroxyanthranilic acid was associated positively with BMD among women only (P ≤ 0·010). In conclusion, we found an inverse association between BMD and markers of IFN-γ-mediated inflammation in the oldest participants. BMD was also associated with two kynurenines in both age groups. These results may support a role of cell-mediated inflammation in bone metabolism.
在炎症性疾病中，骨质疏松症的风险增加。在细胞介导的免疫激活中，干扰素 (IFN)-γ 刺激巨噬细胞释放新蝶呤并增加吲哚胺 2,3-双加氧酶 (IDO) 的活性，从而刺激色氨酸沿犬尿氨酸途径降解。因此，血浆中新蝶呤和犬尿氨酸/色氨酸比值 (KTR) 水平是 IFN-γ 介导的炎症的标志物。几种犬尿氨酸途径代谢物（犬尿氨酸）具有免疫调节特性。本研究旨在探讨 IFN-γ 介导的炎症标志物与骨矿物质密度 (BMD) 之间的关系。该研究基于社区的霍达兰健康研究 (HUSK)，参与者为中年 (46-49 岁) 和老年人 (71-74 岁)，于 1998 年至 2000 年进行 (n=5312)。使用线性和逻辑回归分析研究了与新蝶呤、KTR 和犬尿氨酸相关的髋部 BMD。在最年长的组中，新蝶呤 (P≤0·019) 和 KTR (P≤0·001) 在经过多次调整后与 BMD 呈负相关。在最年长的队列中，与最高四分位数相比，新蝶呤最低四分位数的低 BMD（BMD 最低五分位数）的比值比 (OR) 为男性 2·01 和女性 2·34（P≤0·007），KTR 为男性 1·80 和女性 2·04（P≤0·022）。黄尿酸在所有性别和年龄组中均与 BMD 呈正相关，而 3-羟基犬尿氨酸仅在女性中与 BMD 呈正相关（P≤0·010）。总之，我们发现最年长的参与者中 BMD 与 IFN-γ 介导的炎症标志物呈负相关。在两个年龄组中，BMD 还与两种犬尿氨酸相关。这些结果可能支持细胞介导的炎症在骨代谢中的作用。
