Background and objectives

Modulation of the immune reaction is essential in the development of various diseases, including dengue's “Cytokine Tsunami”, an increase in vascular permeability with concomitant severe vascular leakage. We aim to identify the role of T-helper (Th) cells, Th2 and Th7, with their related cytokines in dengue pathogenesis.

Material and methods

Nine electronic databases and manual search were applied to detect available publications. A meta-analysis using a fixed- or random-effect model was performed to measure standardized mean difference (SMD) with 95% confidence interval (CI). The National Institute of Health (NIH) tools for observational cohort, cross-sectional, and case-control studies were used to examine the risk of bias. The protocol was recorded in PROSPERO with CRD42017060230.

Results

A total of 38 articles were found including 19 case-control, 11 cross-sectional and 8 prospective cohort studies. We indicated that Th2 cytokines (IL-4, IL-6, IL-8) and Th17 cytokine (IL-17) in dengue patients were notably higher than in a healthy control group in acute phase (SMD = 1.59, 95% CI [0.68, 2.51], p = 0.001; SMD = 1.24, 95% CI [0.41, 2.06], p = 0.003; SMD = 1.13, 95% CI [0.61, 1.66], p<0.0001; SMD = 1.74, 95% CI [0.87, 2.61], p<0.0001), respectively.

Conclusions

This study provides evidence of the significant roles of IL-4, IL-6, IL-8, IL-10 and IL-17 in the pathogenesis of developing a severe reaction in dengue fever. However, to fully determine the association of Th cytokines with dengue, it is necessary to perform further studies to assess kinetic levels during the duration of the illness.

中文翻译：

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T辅助免疫调节剂产生的细胞因子在登革热发病中的作用：系统综述和荟萃分析

背景和目标

免疫反应的调节对于各种疾病的发展至关重要，包括登革热的“细胞因子海啸”，即血管通透性的增加以及严重的血管渗漏。我们旨在确定T辅助（Th）细胞，Th2和Th7及其相关的细胞因子在登革热发病机理中的作用。

材料与方法

九个电子数据库和手动搜索被用来检测可用的出版物。进行了使用固定或随机效应模型的荟萃分析，以95％置信区间（CI）衡量标准均值差（SMD）。美国国立卫生研究院（NIH）用于观察性队列研究，横断面研究和病例对照研究的工具用于检查偏倚的风险。该协议已在PROSPERO中使用CRD42017060230进行了记录。

结果

共发现38篇文章，包括19例病例对照，11篇横断面和8篇前瞻性队列研究。我们指出，登革热患者的Th2细胞因子（IL-4，IL-6，IL-8）和Th17细胞因子（IL-17）在急性期显着高于健康对照组（SMD = 1.59，95％CI [ 0.68，2.51]，p  = 0.001; SMD = 1.24，95％CI [0.41，2.06]，p  = 0.003; SMD = 1.13，95％CI [0.61，1.66]，p <0.0001; SMD = 1.74，95％CI [0.87，2.61]，p＜0.0001）。

结论

这项研究提供了IL-4，IL-6，IL-8，IL-10和IL-17在登革热严重反应发展过程中的重要作用的证据。但是，要完全确定Th细胞因子与登革热的关联，有必要进行进一步的研究以评估疾病持续期间的动力学水平。