Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellin, Colombia.
Grupo Inmunovirologia, Facultad de Medicina, Universidad de Antioquia, UdeA, Medellín, Colombia.
PLoS One. 2019 Mar 22;14(3):e0214245. doi: 10.1371/journal.pone.0214245. eCollection 2019.
The triggering of severe dengue has been associated with an exacerbated inflammatory process characterized by the production of pro-inflammatory cytokines such as IL-1β/IL-18, which are the product of inflammasome activation. Furthermore, alteration in the levels of high-density (HDL) and low-density lipoproteins (LDL) has been observed; and HDL are known to have immunomodulatory properties, including the regulation of inflammasomes. While HDL would be expected to counteract hyperactivation of the inflammasome, the relationship between HDL and dengue severity, has not previously been explored.
We conducted a cross-sectional study of 30 patients with dengue and 39 healthy controls matched by sex and age. Lipid profile and levels of C-reactive protein were quantified. Serum levels of IL-1β, IL-6, IL-10, IL-18, and TNF-α, were assessed by ELISA. Expression of inflammasome-related genes in PBMC was quantified by qPCR.
Dengue patients presented an alteration in the parameters of the lipid profile, with a significant decrease in HDL levels, which was more pronounced in dengue patients with warning signs. Moreover, a decrease in the expression of the inflammasome-related genes NLRP1, NLRC4, caspase-1, IL-1β and IL-18 was observed, as well as an increase in serum levels of C-reactive protein and IL-10 in dengue patients versus healthy donors. Significant positive correlations between LDL levels and the relative expression of NLRP3, NLRC4, IL-1β and IL-18, were found.
The results suggest that there is a relationship between the alteration of LDL and HDL with the imbalance in the inflammatory response, which could be associated with the severity of dengue.
严重登革热的发生与炎症反应的加剧有关，其特征是产生促炎细胞因子，如 IL-1β/IL-18，这是炎症小体激活的产物。此外，还观察到高密度脂蛋白（HDL）和低密度脂蛋白（LDL）水平的改变；已知 HDL 具有免疫调节特性，包括对炎症小体的调节。虽然 HDL 预计会对抗炎症小体的过度激活，但 HDL 与登革热严重程度之间的关系尚未得到探索。
我们对 30 例登革热患者和 39 例性别和年龄匹配的健康对照进行了横断面研究。定量测定血脂谱和 C 反应蛋白水平。通过 ELISA 评估血清中 IL-1β、IL-6、IL-10、IL-18 和 TNF-α 的水平。通过 qPCR 定量测定 PBMC 中炎症小体相关基因的表达。
登革热患者的血脂参数发生改变，HDL 水平显著降低，有警告信号的登革热患者更为明显。此外，还观察到炎症小体相关基因 NLRP1、NLRC4、caspase-1、IL-1β 和 IL-18 的表达减少，以及 C 反应蛋白和 IL-10 的血清水平升高在登革热患者与健康供体之间。发现 LDL 水平与 NLRP3、NLRC4、IL-1β 和 IL-18 的相对表达之间存在显著正相关。
结果表明，LDL 和 HDL 的改变与炎症反应失衡之间存在关系，这可能与登革热的严重程度有关。
