Healthy young women with serotonin transporter SS polymorphism show a pro-inflammatory bias under resting and stress conditions.
Healthy young women with serotonin transporter SS polymorphism show a pro-inflammatory bias under resting and stress conditions.
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DOI：
10.1016/j.bbi.2009.10.014
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发表时间：
2010-03
影响因子：
15.1
通讯作者：
Dhabhar, Firdaus S.
中科院分区：
文献类型：
--
作者：
Fredericks, Carolyn A.;Drabant, Emily M.;Edge, Michael D.;Tillie, Jean M.;Hallmayer, Joachim;Ramel, Wiveka;Kuo, Janice R.;Mackey, Sean;Gross, James J.;Dhabhar, Firdaus S.
关键词：
鉴于目前对5-羟色胺转运体基因启动子区(5-HTTLPR)多态性与临床相关性的争论，对其功能相关生物学效应的研究尤为重要。在这里，我们报告了携带两个短(SS)和长(LL)5-HTTLPR等位基因的个体之间的内在免疫生物学差异，这种差异在报告低暴露于生活压力的健康受试者中观察到。鉴于5-HTTLPR基因多态性被认为影响抑郁症的易感性，并与强大的神经生物学效应有关，抑郁症与较高的促炎细胞因子和较低的抗炎细胞因子相关，以及急性应激源增加促炎细胞因子的循环浓度，我们假设与LL-个体相比，SS-个体在静息条件下和/或在应激期间可能表现出促炎倾向。15-LL和11-SS-个体参加了Trier社会压力测试(TSST)。在开始20分钟负荷测试后的30、60、90和120分钟，对血清IL-6和IL-10进行定量。与LL-个体相比，SS-个体在基线和应激期间的IL-6/IL-10比值较高。重要的是，尽管两组人都很健康，在TSST期间报告了相似的压力强度和负面情绪，并报告了类似的早期和近期生活压力的低暴露，但仍观察到了这种促炎倾向。据我们所知，这是首次报道携带5-HTTLPR SS基因的个体存在促炎倾向/表型。因此，健康的SS-个体在休息和应激条件下可能会长期暴露在促炎的生理负担中，这可能会增加他们对抑郁症和其他疾病等疾病的易感性，这些疾病可能会因慢性促炎状态而加剧/加剧。
The study of functionally relevant biological effects of serotonin transporter gene promoter region (5-HTTLPR) polymorphisms is especially important given the current controversy about the clinical relevance of these polymorphisms. Here we report an intrinsic immunobiological difference between individuals carrying two short (SS) versus long (LL) 5-HTTLPR alleles, that is observed in healthy subjects reporting low exposure to life stress. Given that 5-HTTLPR polymorphisms are thought to influence susceptibility to depression and are associated with robust neurobiological effects, that depression is associated with higher pro-inflammatory and lower anti-inflammatory cytokines, and that acute stressors increase circulating concentrations of pro-inflammatory cytokines, we hypothesized that compared to LL-individuals, SS-individuals may show a pro-inflammatory bias under resting conditions and/or during stress. 15-LL and 11-SS-individuals participated in the Trier Social Stress Test (TSST). Serum IL-6 and IL-10 were quantified at baseline and 30, 60, 90, and 120 minutes after beginning the 20-minute stress test. Compared to LL-individuals, SS-individuals showed a higher IL-6/IL-10 ratio at baseline and during stress. Importantly, this pro-inflammatory bias was observed despite both groups being healthy, reporting similar intensities of stress and negative emotionality during the TSST, and reporting similar low exposures to early and recent life stress. To our knowledge, this is the first report of a pro-inflammatory bias/phenotype in individuals carrying the SS genotype of 5-HTTLPR. Thus, healthy SS-individuals may be chronically exposed to a pro-inflammatory physiological burden under resting and stress conditions, which could increase their vulnerability to disorders like depression and other diseases that can be facilitated/exacerbated by a chronic proinflammatory state.
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影响因子：
45.3
作者：
Capuron, L;Ravaud, A;Dantzer, R
通讯作者：
Dantzer, R
影响因子：
3.7
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影响因子：
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Zule, W
影响因子：
11
作者：
Champoux, M;Bennett, A;Suomi, SJ
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Suomi, SJ
影响因子：
10.6
作者：
Capuron, Lucile;Su, Shaoyong;Miller, Andrew H.;Bremner, J. Douglas;Goldberg, Jack;Vogt, Gerald J.;Maisano, Carisa;Jones, Linda;Murrah, Nancy V.;Vaccarino, Viola
通讯作者：
Vaccarino, Viola