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登革热患者在不同病程阶段的细胞因子表达谱。

Cytokine expression profile of dengue patients at different phases of illness.

机构信息

Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

出版信息

PLoS One. 2012;7(12):e52215. doi: 10.1371/journal.pone.0052215. Epub 2012 Dec 20.

Abstract

BACKGROUND

Dengue is an important medical problem, with symptoms ranging from mild dengue fever to severe forms of the disease, where vascular leakage leads to hypovolemic shock. Cytokines have been implicated to play a role in the progression of severe dengue disease; however, their profile in dengue patients and the synergy that leads to continued plasma leakage is not clearly understood. Herein, we investigated the cytokine kinetics and profiles of dengue patients at different phases of illness to further understand the role of cytokines in dengue disease.

METHODS AND FINDINGS

Circulating levels of 29 different types of cytokines were assessed by bead-based ELISA method in dengue patients at the 3 different phases of illness. The association between significant changes in the levels of cytokines and clinical parameters were analyzed. At the febrile phase, IP-10 was significant in dengue patients with and without warning signs. However, MIP-1β was found to be significant in only patients with warning signs at this phase. IP-10 was also significant in both with and without warning signs patients during defervescence. At this phase, MIP-1β and G-CSF were significant in patients without warning signs, whereas MCP-1 was noted to be elevated significantly in patients with warning signs. Significant correlations between the levels of VEGF, RANTES, IL-7, IL-12, PDGF and IL-5 with platelets; VEGF with lymphocytes and neutrophils; G-CSF and IP-10 with atypical lymphocytes and various other cytokines with the liver enzymes were observed in this study.

CONCLUSIONS

The cytokine profile patterns discovered between the different phases of illness indicate an essential role in dengue pathogenesis and with further studies may serve as predictive markers for progression to dengue with warning signs.

摘要

背景

登革热是一个重要的医学问题,其症状从轻症登革热到严重形式不等,严重形式下血管渗漏会导致低血容量性休克。细胞因子被认为在重症登革热疾病的进展中发挥作用;然而,它们在登革热患者中的特征以及导致持续血浆渗漏的协同作用尚不清楚。在此,我们研究了不同疾病阶段登革热患者的细胞因子动力学和特征,以进一步了解细胞因子在登革热疾病中的作用。

方法和发现

通过 bead-based ELISA 方法评估了 29 种不同类型细胞因子在登革热患者不同疾病阶段的循环水平。分析了细胞因子水平的显著变化与临床参数之间的关联。在发热期,IP-10 在有和无症状的登革热患者中均显著。然而,MIP-1β 仅在有警告症状的患者中在该阶段显著。在退热期,IP-10 在有和无症状的患者中均显著。在该阶段,MIP-1β 和 G-CSF 在无警告症状的患者中显著,而 MCP-1 在有警告症状的患者中显著升高。在这项研究中观察到 VEGF、RANTES、IL-7、IL-12、PDGF 和 IL-5 与血小板之间存在显著相关性;VEGF 与淋巴细胞和中性粒细胞之间存在显著相关性;G-CSF 和 IP-10 与非典型淋巴细胞之间存在显著相关性,以及各种其他细胞因子与肝酶之间存在显著相关性。

结论

不同疾病阶段之间发现的细胞因子特征模式表明其在登革热发病机制中具有重要作用,进一步的研究可能成为具有警告症状的登革热进展的预测标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91ba/3527385/37aec8e45a13/pone.0052215.g001.jpg

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