Inflammatory status and severity of disease in dengue patients are associated with lipoprotein alterations

PLoS One. 2019 Mar 22;14(3):e0214245. doi: 10.1371/journal.pone.0214245. eCollection 2019.

Abstract

Introduction: 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.

Methodology: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • C-Reactive Protein / analysis
  • Cross-Sectional Studies
  • Dengue / blood*
  • Female
  • Humans
  • Inflammation / blood*
  • Interleukin-10 / blood
  • Interleukin-18 / blood
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Lipoproteins, HDL / blood*
  • Lipoproteins, LDL / blood*
  • Male
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha / blood

Substances

  • IL10 protein, human
  • IL1B protein, human
  • Interleukin-18
  • Interleukin-1beta
  • Interleukin-6
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • C-Reactive Protein

Associated data

  • figshare/10.6084/m9.figshare.7675643

Grants and funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by Colciencias Grant 141565741029, Universidad Cooperativa de Colombia and Universidad de Antioquia UdeA. The funder had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.