Decreased circulating macrophage migration inhibitory factor (MIF) protein and blood mononuclear cell MIF transcripts in children with Plasmodium falciparum malaria

Decreased circulating macrophage migration inhibitory factor (MIF) protein and blood mononuclear cell MIF transcripts in children with Plasmodium falciparum malaria
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DOI:
10.1016/j.clim.2005.12.003
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发表时间:
2006-05-01
影响因子:
8.6
通讯作者:
Perkins, DJ
Perkins, DJ
中科院分区:
医学3区
文献类型:
--
作者:
Awandare, GA;Hittner, JB;Perkins, DJ

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恶性疟原虫疟疾仍然是影响撒哈拉以南非洲儿童的最常见致命疾病之一,但调节发病机制的免疫介质仅部分确定。巨噬细胞迁移抑制因子(macrophage migration inhibitory factor, MIF)在调节细菌先天免疫中起重要作用。研究了急性恶性疟疾儿童的寄生虫感染、循环MIF和外周血单核细胞(PBMC) MIF转录本。同时测定外周血中mif调节细胞因子及效应分子水平,包括干扰素(IFN)- γ、肿瘤坏死因子(TNF)- α、白细胞介素(IL)-12、IL-10、转化生长因子(TGF)- β 1、双环前列腺素(PG) E-2、一氧化氮合酶活性。急性疟疾儿童的循环MIF和PBMC MIF mRNA明显低于健康疟疾暴露儿童。外周血MIF水平与寄生虫血症或血红蛋白浓度均无相关性。然而,循环MIF与IL-12和tgf - β 1显著相关。多元回归分析显示,ifn - γ是外周血MIF浓度最显著的预测因子。这些发现表明,减少MIF的产生可能会提高恶性疟疾儿童的疾病严重程度。(c) 2006爱思唯尔公司版权所有。
Plasmodium falciparum malaria remains one of the most frequently lethal diseases affecting children in sub-Saharan Africa, yet the immune mediators that regulate pathogenesis are only partially defined. Since macrophage migration inhibitory factor (MIF) is important for regulating innate immunity in bacterial. and parasitic infections, circulating MIF and peripheral blood mononuclear cell (PBMC) MIF transcripts were investigated in children with acute falciparum malaria. Peripheral blood levels of MIF-regutatory cytokines and effector molecules, including interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-12, IL-10, transforming growth factor (TGF)-beta 1, bicyclo-prostagiandin (PG) E-2, and nitric oxide synthase activity were also determined. Circulating MIF and PBMC MIF mRNA were significantly lower in children with acute malaria relative to healthy, malaria-exposed children. Peripheral blood MIF levels showed no association with either parasitemia or hemoglobin concentrations. Circulating MIF was, however, significantly associated with IL-12 and TGF-beta 1. Multiple regression analyses revealed that IFN-gamma was the most significant predictor of peripheral blood MIF concentrations. These findings suggest that reduced MIF production may promote enhanced disease severity in children with falciparum malaria. (c) 2006 Elsevier Inc. All rights reserved.