Seattle Biomedical Research Institute, Seattle, Washington, USA.
Infect Immun. 2012 Sep;80(9):3034-8. doi: 10.1128/IAI.00220-12. Epub 2012 Jun 11.
Placental infection with Plasmodium falciparum is associated with increased levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ), and previous studies have associated increased levels of these cytokines with low birth weight (LBW), especially for malaria-infected primigravidae. To define the contribution of TNF-α and IFN-γ networks to placental-malaria-associated LBW, we measured chemokines induced by TNF-α and IFN-γ and related them to birth weight in a birth cohort of 782 mother-infant pairs residing in an area of P. falciparum holoendemicity in Tanzania. Among primigravidae, levels of CCL2, CXC ligand 9 (CXCL9), and CXCL13 were significantly higher during malaria infection in both the placenta and peripheral blood. Placental CXCL9 and CXCL13 levels were also higher in placental blood from secundigravidae and multigravidae. In multivariate analyses adjusted for known predictors of birth weight, malaria-infected primigravidae with placental CXCL9 levels in the lowest tertile gave birth to babies who weighed 610 g more than babies born to mothers with high CXCL9 levels. CXCL9 expression is induced by IFN-γ, and the strong association between birth weight and placental CXCL9 is consistent with previous observations relating IFN-γ to poor pregnancy outcomes.
胎盘感染疟原虫与促炎细胞因子水平升高有关，包括肿瘤坏死因子-α（TNF-α）和γ干扰素（IFN-γ），先前的研究表明这些细胞因子水平升高与低出生体重（LBW）有关，尤其是对感染疟原虫的初产妇。为了确定 TNF-α 和 IFN-γ 网络对胎盘疟疾相关 LBW 的贡献，我们测量了 TNF-α 和 IFN-γ 诱导的趋化因子，并在坦桑尼亚疟疾流行地区的 782 对母婴队列中，将其与出生体重相关联。在初产妇中，胎盘和外周血中的 CCL2、CXCL9 和 CXCL13 水平在疟疾感染期间均显著升高。在经产次和多胎次产妇的胎盘血中，胎盘 CXCL9 和 CXCL13 水平也更高。在调整了已知出生体重预测因素的多变量分析中，胎盘 CXCL9 水平处于最低三分位数的疟疾感染初产妇所生婴儿的体重比 CXCL9 水平较高的母亲所生婴儿重 610 克。CXCL9 的表达受 IFN-γ 诱导，出生体重与胎盘 CXCL9 之间的强烈关联与先前观察到 IFN-γ 与不良妊娠结局有关的结果一致。
