Zhang Long, Brown Todd T, Margolick Joseph B, Witt Mallory D, Palella Frank J, Kingsley Lawrence A, Hoofnagle Andrew N, Tin Adrienne, Jacobson Lisa P, Abraham Alison G
1 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland.
2 Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University School of Medicine , Baltimore, Maryland.
AIDS Res Hum Retroviruses. 2018 Oct 30;34(12):1067-74. doi: 10.1089/AID.2018.0101.
The inflammatory context of HIV infection has been posited to contribute to the higher comorbidity risk noted in HIV-infected populations. One possible pathway may involve 1,25-dihydroxyvitamin D [1,25(OH)D], which plays a wide biologic role in many tissues. We sought to investigate whether inflammation was associated with vitamin D metabolites in a cohort of HIV-infected (HIV+) men receiving treatment and HIV-uninfected (HIV-) men. Vitamin D metabolites, including 25-hydroxyvitamin D [25(OH)D] and 1,25(OH)D, were measured along with 24 inflammatory markers among Multicenter AIDS Cohort Study participants. Exploratory factor analysis reduced inflammatory marker data to a smaller set of inflammatory processes (IPs). Multivariate linear regression was used to evaluate associations between vitamin D metabolites and IPs. There were 466 HIV+ and 100 HIV- men, who contributed 658 stored samples from 1998 to 2008. We found three IPs with IP 1 characterized by sTNF-R2, sIL-2Rα, sCD27, BAFF, sgp130, sCD14, CXCL10 (IP-10), and sIL-6R. While none of the three IPs was associated with 25(OH)D levels in either HIV+ or HIV-, higher levels of IP 1 were significantly associated with the reduced levels of 1,25(OH)D in HIV+, and a similar although nonsignificant trend was seen in HIV-. The association between 1,25(OH)D and inflammation found among HIV-infected men suggests a possible mechanism whereby inflammation leads to the increased comorbidity risk noted among HIV-infected individuals.
HIV感染的炎症背景被认为是导致HIV感染人群中较高合并症风险的原因之一。一条可能的途径可能涉及1,25-二羟基维生素D [1,25(OH)D]，它在许多组织中发挥着广泛的生物学作用。我们试图研究在接受治疗的HIV感染（HIV+）男性和未感染HIV（HIV-）男性队列中，炎症是否与维生素D代谢产物相关。在多中心艾滋病队列研究参与者中，测量了维生素D代谢产物，包括25-羟基维生素D [25(OH)D]和1,25(OH)D，以及24种炎症标志物。探索性因子分析将炎症标志物数据简化为一组较小的炎症过程（IPs）。使用多元线性回归来评估维生素D代谢产物与IPs之间的关联。共有466名HIV+男性和100名HIV-男性，他们在1998年至2008年期间提供了658份储存样本。我们发现了三个IPs，其中IP 1的特征是可溶性肿瘤坏死因子受体2（sTNF-R2）、可溶性白细胞介素-2受体α（sIL-2Rα）、可溶性CD27、B细胞活化因子（BAFF）、可溶性糖蛋白130（sgp130）、可溶性CD14、CXC趋化因子配体10（IP-10）和可溶性白细胞介素-6受体（sIL-6R）。虽然这三个IPs在HIV+或HIV-男性中均与25(OH)D水平无关，但IP 1水平较高与HIV+男性中1,25(OH)D水平降低显著相关，在HIV-男性中也观察到了类似但不显著的趋势。在HIV感染男性中发现的1,25(OH)D与炎症之间的关联表明了一种可能的机制，即炎症导致了HIV感染个体中合并症风险增加。
