The Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Am J Respir Crit Care Med. 2010 Jul 1;182(1):25-33. doi: 10.1164/rccm.200904-0637OC. Epub 2010 Mar 1.
Stress-elicited disruption of immunity begins in utero.
Associations among prenatal maternal stress and cord blood mononuclear cell (CBMC) cytokine responses were prospectively examined in the Urban Environment and Childhood Asthma Study (n = 557 families).
Prenatal maternal stress included financial hardship, difficult life circumstances, community violence, and neighborhood/block and housing conditions. Factor analysis produced latent variables representing three contexts: individual stressors and ecological-level strains (housing problems and neighborhood problems), which were combined to create a composite cumulative stress indicator. CBMCs were incubated with innate (lipopolysaccharide, polyinosinic-polycytidylic acid, cytosine-phosphate-guanine dinucleotides, peptidoglycan) and adaptive (tetanus, dust mite, cockroach) stimuli, respiratory syncytial virus, phytohemagglutinin, or medium alone. Cytokines were measured using multiplex ELISAs. Using linear regression, associations among increasing cumulative stress and cytokine responses were examined, adjusting for sociodemographic factors, parity, season of birth, maternal asthma and steroid use, and potential pathway variables (prenatal smoking, birth weight for gestational age).
Mothers were primarily minorities (Black [71%], Latino [19%]) with an income less than $15,000 (69%). Mothers with the highest cumulative stress were older and more likely to have asthma and deliver lower birth weight infants. Higher prenatal stress was related to increased IL-8 production after microbial (CpG, PIC, peptidoglycan) stimuli and increased tumor necrosis factor-alpha to microbial stimuli (CpG, PIC). In the adaptive panel, higher stress was associated with increased IL-13 after dust mite stimulation and reduced phytohemagglutinin-induced IFN-gamma.
Prenatal stress was associated with altered innate and adaptive immune responses in CBMCs. Stress-induced perinatal immunomodulation may impact the expression of allergic disease in these children.
应激引起的免疫紊乱始于宫内。
本研究前瞻性地观察了城市环境与儿童哮喘研究(n=557 个家庭)中产前母体应激与脐血单个核细胞(CBMC)细胞因子反应之间的关联。
产前母体应激包括经济困难、生活困难、社区暴力以及邻里/街区和住房条件。因子分析产生了代表三个背景的潜在变量:个体应激源和生态水平压力(住房问题和邻里问题),将其结合起来创建一个复合累积应激指标。用内源性(脂多糖、聚肌苷酸-聚胞苷酸、胞嘧啶-磷酸-鸟嘌呤二核苷酸、肽聚糖)和适应性(破伤风、尘螨、蟑螂)刺激物、呼吸道合胞病毒、植物血凝素或培养基孵育 CBMC。采用多重 ELISA 法测定细胞因子。采用线性回归,调整社会人口因素、产次、出生季节、母亲哮喘和类固醇使用以及潜在途径变量(产前吸烟、出生体重与胎龄比)后,分析累积应激增加与细胞因子反应之间的关系。
母亲主要是少数民族(黑人[71%],拉丁裔[19%]),收入低于 15000 美元(69%)。累积应激最高的母亲年龄较大,更有可能患有哮喘,且婴儿出生体重较低。较高的产前应激与微生物(CpG、PIC、肽聚糖)刺激后 IL-8 的产生增加以及微生物刺激(CpG、PIC)后 TNF-α增加有关。在适应性面板中,较高的应激与尘螨刺激后 IL-13 的增加和植物血凝素诱导的 IFN-γ减少有关。
产前应激与 CBMC 中固有和适应性免疫反应的改变有关。应激诱导的围产期免疫调节可能影响这些儿童过敏性疾病的表达。