Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria.

Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria.
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DOI:
10.1128/cvi.00533-16
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发表时间:
2017-04
期刊:
Clinical and vaccine immunology : CVI
影响因子:
--
通讯作者:
MacLennan CA
MacLennan CA
中科院分区:
其他
文献类型:
--
作者:
Mandala WL;Msefula CL;Gondwe EN;Drayson MT;Molyneux ME;MacLennan CA

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促炎性细胞因子参与恶性疟原虫的清除,并且非常高水平的这些细胞因子已经与严重疟疾的发病机制有关。为了确定细胞因子如何随疾病严重程度和综合征而变化,我们招募了患有脑型疟疾(CM)、严重疟疾性贫血(SMA)和单纯性疟疾(UCM)的马拉维儿童和健康对照。我们分析了急性感染和恢复期的血清细胞因子浓度。除白细胞介素5(IL-5)外,急性CM中细胞因子浓度最高,其次是SMA,UCM中仅轻度升高。在所有三个临床疟疾组中,在恢复期1个月时重新测量时,细胞因子浓度已降至对照水平。IL-10与肿瘤坏死因子α(TNF-α)和IL-10与IL-6的比值遵循相似的模式。急性CM患儿血清中TNF-α(P < 0.001)、IFN-γ(P = 0.0019)、IL-2(P = 0.0004)、IL-6(P <0.001)、IL-8(P < 0.001)和IL-10(P < 0.001)浓度显著高于健康对照组。急性CM患者的IL-6(P < 0.001)和IL-10(P = 0.0003)浓度显著高于急性SMA患者。我们的研究结果是一致的概念,高水平的促炎细胞因子,尽管高水平的抗炎细胞因子IL-10,可能有助于CM的发病机制。
Proinflammatory cytokines are involved in clearance of Plasmodium falciparum, and very high levels of these cytokines have been implicated in the pathogenesis of severe malaria. In order to determine how cytokines vary with disease severity and syndrome, we enrolled Malawian children presenting with cerebral malaria (CM), severe malarial anemia (SMA), and uncomplicated malaria (UCM) and healthy controls. We analyzed serum cytokine concentrations in acute infection and in convalescence. With the exception of interleukin 5 (IL-5), cytokine concentrations were highest in acute CM, followed by SMA, and were only mildly elevated in UCM. Cytokine concentrations had fallen to control levels when remeasured at 1 month of convalescence in all three clinical malaria groups. Ratios of IL-10 to tumor necrosis factor alpha (TNF-α) and of IL-10 to IL-6 followed a similar pattern. Children presenting with acute CM had significantly higher concentrations of TNF-α (P < 0.001), interferon gamma (IFN-γ) (P = 0.0019), IL-2 (P = 0.0004), IL-6 (P < 0.001), IL-8 (P < 0.001), and IL-10 (P < 0.001) in sera than healthy controls. Patients with acute CM had significantly higher concentrations of IL-6 (P < 0.001) and IL-10 (P = 0.0003) than those presenting with acute SMA. Our findings are consistent with the concept that high levels of proinflammatory cytokines, despite high levels of the anti-inflammatory cytokine IL-10, could contribute to the pathogenesis of CM.