ELEVATED TUMOR NECROSIS FACTOR-ALPHA AND INTERLEUKIN-6 SERUM LEVELS AS MARKERS FOR COMPLICATED PLASMODIUM-FALCIPARUM MALARIA
ELEVATED TUMOR NECROSIS FACTOR-ALPHA AND INTERLEUKIN-6 SERUM LEVELS AS MARKERS FOR COMPLICATED PLASMODIUM-FALCIPARUM MALARIA
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DOI：
10.1016/s0002-9343(89)80688-6
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发表时间：
1989-08-01
影响因子：
5.9
通讯作者：
DIETRICH, M
中科院分区：
文献类型：
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作者：
KERN, P;HEMMER, CJ;DIETRICH, M
肿瘤坏死因子α（TNF-α）与实验性疟疾的病理学有关。为了确定其与人类疟疾的相关性，我们研究了疟疾患者在抗寄生虫治疗之前和治疗期间两种单核细胞衍生的细胞因子 TNF-α 和白介素 6 (IL-6) 以及淋巴细胞衍生的介质干扰素 γ (IFN-gamma) 的血清水平。对 40 名疟疾患者（恶性疟原虫 [n = 32]、间日疟原虫 [n = 8]）的 120 份血清样本进行了分析。 IL-6通过高度灵敏和特异的生物测定法测定，TNF-α通过免疫放射测定法测定，IFN-γ通过放射免疫测定法测定。大多数恶性疟患者在治疗前可检测到细胞因子水平升高（TNF-α、IL-6 和 IFN-γ 分别为 32 例中的 31 例、32 例中的 21 例和 32 例中的 21 例），但仅在部分间日疟患者中检测到（TNF-α、IL-6 和 IFN-γ 分别为 8 例中的 4 例、8 例中的 1 例和 8 例中的 0 例）。单核因子 TNF-α 和 IL-6 的血清浓度与寄生虫密度显着相关 (p < 0.001)。与循环 IFN-γ 浓度没有获得这种相关性。 18 例临床病程复杂的恶性疟原虫感染患者中，单核因子 TNF-α 和 IL-6 水平显着升高（TNF-α 中位数为 172 mg·mL，IL-6 U/mL，峰值分别为 896 pg/mL 和 1,000 U/mL）。血清中 TNF-α 和 IL-6 浓度之间的相关性（n = 40，r = 0.56，p = 0.0002）表明这些介质的协调产生。研究发现，人类疟疾的器官损伤与循环细胞因子 TNF-α 和 IL-6 的水平相关。因此，未经治疗的恶性疟原虫感染中细胞因子网络的不平衡可作为疾病严重程度的标志。细胞因子反应的调节可能代表一种治疗人类疟疾严重器官功能障碍的新方法。
Tumor necrosis factor alpha (TNF-alpha) has been implicated in the pathology of experimental malaria. To establish its relavance to human malaria, we studied serum levels of two monocyte-derived cytokines, TNF-alpha and interleukin-6 (IL-6), as well as of the lymphocyte-derived mediator interferon gamma (IFN-gamma) in patients with malaria before and during antiparasitic treatment. One hundred twenty serum samples of 40 patients with malaria (Palsmodium falciparum [n = 32], Plasmodium vivax [n = 8]) were analyzed. IL-6 was measured by a highly sensitive and specific bioassay, TNF-alpha by immunoradiometric assay, and IFN-gamma by radioimmunoassay. Elevated cytokine levels could be detected in the majority of patients with P. falciparum malaria before treatment (31 of 32, 21 of 32, and 21 of 32 for TNF-alpha, IL-6, and IFN-gamma, respectively), but only in some patients with P. vivax malaria (four of eight, one of eight, and zero of eight for TNF-alpha, IL-6, and IFN-gamma, respectively). Serum concentrations of the monokines TNF-alpha and IL-6 correlated significantly with parasitic density (p < 0.001). No such correlation was obtained with the circulating IFN-gamma concentration. The levels of monokines TNF-alpha and IL-6 were markedly elevated in 18 P. falciparum-infected patients with complicated clinical courses (median values for TNF-alpha 172 mg.mL, for IL-6 U/mL, peak values: 896 pg/mL and 1,000 U/mL, respectively). The correlation between TNF-alpha and IL-6 concentrations in serum (n = 40, r = 0.56, p = 0.0002) suggests co-ordinate production of those mediators. Organ impairment in human malaria was found to be correlated with the amount of circulating cytokine levels of TNF-alpha and IL-6. Thus, imbalance of the cytokine network in untreated P. falciparum infection serve as markers of severity of disease. Modulation of cytokine response could represent a novel approach to the treatment of severe organ dysfunction in human malaria.