Disease Severity in Patients Infected with Leishmania mexicana Relates to IL-1β
Disease Severity in Patients Infected with Leishmania mexicana Relates to IL-1β
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DOI：
10.1371/journal.pntd.0001533
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发表时间：
2012-05-01
影响因子：
3.8
通讯作者：
Becker, Ingeborg
中科院分区：
文献类型：
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作者：
Fernandez-Figueroa, Edith A.;Rangel-Escareno, Claudia;Becker, Ingeborg
墨西哥利什曼原虫可引起局限性（LCL）和弥漫性（DCL）皮肤利什曼病，但人们对调节这些患者疾病严重程度的因素知之甚少。我们在 58 名患有 LCL 的墨西哥混血患者、6 名患有 DCL 的墨西哥混血患者和 123 名对照病例中分析了该疾病是否与 IL-1 beta (-511)、CXCL8 (-251) 和/或抑制剂 IL-1RA (+2018) 的单核苷酸多态性 (SNP) 相关。此外，我们还分析了单核细胞体外产生IL-1β、这些患者血清中该细胞因子的表达，以及LCL和DCL患者皮损中IL-1β的组织分布和寄生虫数量。我们的结果显示，相对于参考组 CC，患者和对照（杂合 OR）之间的 IL-1 beta (-511 C/T) 基因型分布存在显着差异，参考组 CC 的估计值为 3.23，95% CI = (1.2, 8.7) 和 p 值 = 0.0167），表明 IL-1 beta (-511 C/T) 是影响疾病发生风险的变量。感染墨西哥利什曼原虫的患者。此外，单核细胞体外产生IL-1β的增加以及细胞因子血清表达的增加与疾病的严重程度相关，因为在严重感染墨西哥利什曼原虫的DCL患者中，IL-1β的表达显着较高。 IL-1β在病变中的分布也根据组织中寄生虫的数量而变化：在严重感染的LCL患者和所有DCL患者中，细胞因子分散在整个病变中。相比之下，在病变中寄生虫数量较少的 LCL 患者中，IL-1β 仅限于细胞内。这些数据表明 IL-1 β 可能是决定 DCL 患者疾病严重程度的关键因素。 CXCL8和IL-1RA多态性分析显示，不同疾病严重程度的患者之间以及患者与对照之间没有差异。
Leishmania mexicana can cause both localized (LCL) and diffuse (DCL) cutaneous leishmaniasis, yet little is known about factors regulating disease severity in these patients. We analyzed if the disease was associated with single nucleotide polymorphisms (SNPs) in IL-1 beta (-511), CXCL8 (-251) and/or the inhibitor IL-1RA (+2018) in 58 Mexican mestizo patients with LCL, 6 with DCL and 123 control cases. Additionally, we analyzed the in vitro production of IL-1 beta by monocytes, the expression of this cytokine in sera of these patients, as well as the tissue distribution of IL-1 beta and the number of parasites in lesions of LCL and DCL patients. Our results show a significant difference in the distribution of IL-1 beta (-511 C/T) genotypes between patients and controls (heterozygous OR), with respect to the reference group CC, which was estimated with a value of 3.23, 95% CI = (1.2, 8.7) and p-value = 0.0167), indicating that IL-1 beta (-511 C/T) represents a variable influencing the risk to develop the disease in patients infected with Leishmania mexicana. Additionally, an increased in vitro production of IL-1 beta by monocytes and an increased serum expression of the cytokine correlated with the severity of the disease, since it was significantly higher in DCL patients heavily infected with Leishmania mexicana. The distribution of IL-1 beta in lesions also varied according to the number of parasites harbored in the tissues: in heavily infected LCL patients and in all DCL patients, the cytokine was scattered diffusely throughout the lesion. In contrast, in LCL patients with lower numbers of parasites in the lesions, IL-1 beta was confined to the cells. These data suggest that IL-1 beta possibly is a key player determining the severity of the disease in DCL patients. The analysis of polymorphisms in CXCL8 and IL-1RA showed no differences between patients with different disease severities or between patients and controls.