Clusters of cytokines determine malaria severity in Plasmodium falciparum -: Infected patients from endemic areas of central India
Clusters of cytokines determine malaria severity in Plasmodium falciparum -: Infected patients from endemic areas of central India
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DOI：
10.1086/504720
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发表时间：
2006-07-15
影响因子：
6.4
通讯作者：
Pied, Sylviane
中科院分区：
文献类型：
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作者：
Prakash, D.;Fesel, Constantin;Pied, Sylviane
我们研究了干扰素（IFN）-γ、白细胞介素（IL）-1 β、IL-2、IL-4、IL-5、IL-6、IL-10、IL-12、肿瘤坏死因子（TNF）-α和转化生长因子（TGF）-β在临床明确定义的恶性疟原虫感染患者中的作用，这些患者表现为轻度疟疾（MM）、重度非脑型疟疾（SM）、或脑型疟疾（CM），以及来自Gondia（印度疟疾流行地）的对照受试者，以及来自非疟疾流行地区的健康受试者。双向耦合聚类分析显示2个与疾病临床亚组相关的细胞因子簇。第一组由IFN-γ、IL-2、IL-5、IL-6和IL-12组成，其水平在感染期间显著增加，但在MM患者中占主导地位，使我们能够将其与SM或CM患者区分开来。第二个聚类由TGF-β、TNF-α、IL-10和IL-1 β组成，其水平在不同临床组的患者中彼此高度相关，并且随着疾病严重程度显著增加，特别是在CM中。判别分析使我们能够提出一个最小的模型。细胞因子如IL-5、IL-1b、IL-10和IL-2的水平随着感染而增加。IL-12、IL-5和IL-6的水平将严重形式的疟疾与MM区分开。最后，IL-1 β、IL-12和IFN-γ的水平与CM与SM的区分有关：高IL-1 β水平与CM相关，高IL-12和IFN-γ水平与SM相关。
We investigated the role of interferon (IFN)-gamma, interleukin (IL)-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)-beta in clinically well-defined groups of Plasmodium falciparum-infected patients manifesting mild malaria (MM), severe noncerebral malaria (SM), or cerebral malaria (CM) and in control subjects from Gondia, a malaria-endemic site in India, as well as in healthy subjects from non-malaria-endemic areas. Two-way coupled cluster analysis revealed 2 clusters of cytokines relevant to clinical subgroups of disease. The first cluster was composed of IFN-gamma, IL-2, IL-5, IL-6, and IL-12, the levels of which were significantly increased during infection but were predominant in patients with MM and allowed us to distinguish them from patients with SM or CM. The second cluster was composed of TGF-beta, TNF-alpha, IL-10, and IL-1 beta, the levels of which were highly correlated with each other in the different clinical groups of patients and significantly increased with disease severity, particularly in CM. Discriminant analyses allowed us to propose a minimal model. Levels of cytokines such as IL-5, IL-1b, IL-10, and IL-2 increase with infection. Levels of IL-12, IL-5, and IL-6 discriminate severe forms of malaria from MM. Finally, levels of IL-1 beta, IL-12, and IFN-gamma are relevant for the discrimination of CM from SM: high IL-1 beta levels are associated with CM, and high IL-12 and IFN-gamma levels are associated with SM.