Interferon gamma (IFN-γ)-mediated inflammation and the kynurenine pathway in relation to risk of hip fractures: the Hordaland Health Study
Interferon gamma (IFN-γ)-mediated inflammation and the kynurenine pathway in relation to risk of hip fractures: the Hordaland Health Study
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DOI：
10.1007/s00198-014-2720-7
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发表时间：
2014-08-01
影响因子：
4
通讯作者：
Tell, G. S.
中科院分区：
文献类型：
--
作者：
Apalset, E. M.;Gjesdal, C. G.;Tell, G. S.
细胞因子干扰素γ（IFN-γ）通过犬尿氨酸途径刺激新蝶呤释放和色氨酸降解成犬尿氨酸。高水平的新蝶呤与髋部骨折风险增加相关，一些犬尿氨酸也是如此，这表明IFN-γ介导的炎症在导致髋部骨折的过程中起作用。干扰素γ（IFN-γ）启动巨噬细胞释放新蝶呤，还刺激色氨酸沿着犬尿氨酸途径降解，作为细胞介导的免疫活化的一部分。因此，血浆新蝶呤和犬尿氨酸/色氨酸比率（KTR）是IFN-γ介导的炎症的标志物。髋关节骨折的风险与犬尿氨酸途径中的炎症和代谢物（犬尿氨酸）的标记物有关。参与者（71 - 74岁，N = 3，311）在基于社区的Hordaland健康研究（HUSK）中，从招募（1998-2000）到2009年12月31日随访髋关节骨折。采用考克斯比例风险回归分析研究了血浆C-反应蛋白（CRP）、新蝶呤、KTR和6种犬尿氨酸作为髋部骨折的预测因子。与新蝶呤的最低四分位数相比，髋部骨折的风险比（HR）为1.9（95%置信区间（CI）1.3-2.7）（四分位数之间的p趋势< 0.001）。CRP和KTR与髋部骨折风险无关。在犬尿氨酸中，与邻氨基苯甲酸和3-羟基犬尿氨酸的最低四分位数相比，在最高四分位数中发现了更高的骨折风险。对于新蝶呤、CRP和KTR处于最高四分位数的受试者，与未处于最高四分位数的受试者相比，HR为2.5（95%CI 1.6-4.0）。这可能表明低度免疫激活在导致髋部骨折的致病过程中的作用。
The cytokine interferon gamma (IFN-gamma) stimulates neopterin release and tryptophan degradation into kynurenines through the kynurenine pathway. High levels of neopterin were associated with increased hip fracture risk, as were some of the kynurenines, suggesting a role of IFN-gamma-mediated inflammation in the processes leading to hip fracture.Low-grade systemic inflammation has been associated with bone loss and risk of fractures. Interferon gamma (IFN-gamma) initiates macrophage release of neopterin and also stimulates degradation of tryptophan along the kynurenine pathway as part of cell-mediated immune activation. Plasma neopterin and the kynurenine/tryptophan ratio (KTR) are thus markers of IFN-gamma-mediated inflammation. Risk of hip fracture was investigated in relation to markers of inflammation and metabolites in the kynurenine pathway (kynurenines).Participants (71 to74 years, N = 3,311) in the community-based Hordaland Health Study (HUSK) were followed for hip fractures from enrolment (1998-2000) until 31 December 2009. Plasma C-reactive protein (CRP), neopterin, KTR, and six kynurenines were investigated as predictors of hip fracture, using Cox proportional hazards regression analyses.A hazard ratio (HR) of 1.9 (95 % confidence interval (CI) 1.3-2.7) for hip fracture was found in the highest compared to the lowest quartile of neopterin (p trend across quartiles < 0.001). CRP and KTR were not related to hip fracture risk. Among the kynurenines, a higher risk of fracture was found in the highest compared to the lowest quartiles of anthranilic acid and 3-hydroxykynurenine. For subjects in the highest quartiles of neopterin, CRP, and KTR compared to those in no top quartiles, HR was 2.5 (95 % CI 1.6-4.0).This may indicate a role for low-grade immune activation in the pathogenic processes leading to hip fracture.