Previous studies have shown a relationship between circulating lipids and dengue virus infection; however, the association of altered lipid profiles with severe dengue remains little studied. The aim of this study was to determine the association between circulating lipid content and severe dengue and/or platelet counts. Ninety-eight patients (2-66 years old) classified as having dengue without warning signs (DNWS), dengue with warning signs (DWWS), or severe dengue (SD) and 62 healthy individuals were studied. Blood samples were tested for NS1, anti-dengue IgM, platelet content, total cholesterol (TC), triglycerides (T), high-density lipoproteins (HDL), low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL). Lipid alterations were observed mainly in patients with SD. Increased T and VLDL was observed in SD, and increased HDL was observed in DWWS and SD. Decreased TC was found in all forms of dengue, and the lowest LDL values were found in SD. Platelet counts were significantly decreased in DWWS and SD when compare to DNWS. A positive correlation (p = 0.019) between LDL values and platelet counts and a negative correlation (p = 0.0162) between VLDL values and platelet counts were found. Lipid profile alterations were associated with severe dengue.

The role of angiotensin II (Ang II) in dengue virus infection remains unknown. The aim of this study was to determine the effect of losartan, an antagonist of the angiotensin II type 1 receptor (AT1 receptor), and enalapril, an inhibitor of angiotensin I-converting enzyme (ACE), on viral antigen expression and IL-1β production in peritoneal macrophages infected with dengue virus type 2. Mice treated with losartan or enalapril and untreated controls were infected intraperitoneally with the virus, and macrophages were analyzed. Infection resulted in increased IL-1β production and a high percentage of cells expressing viral antigen, and this was decreased by treatment with anti-Ang II drugs, suggesting a role for Ang II in dengue virus infection.

Activated monocytes/macrophages that produce a cytokine storm play an important role in the pathogenesis of dengue. Interleukin-18 (IL-18) is a proinflammatory cytokine produced by monocyte/macrophages that is increased during dengue. Ferritin is an acute-phase reactant and expressed by cells of the reticulo-endothelial system in response to infection by dengue virus. The aims of this study were to analyze the simultaneous expression of both IL-18 and ferritins in children infected by diverse serotypes of dengue virus (DENV) and determine their association with dengue severity. In this regard, children with dengue (n = 25) and healthy controls with similar age and sex (n = 20) were analyzed for circulating ferritin and cytokines. Monocytes were isolated by Hystopaque gradient and co-cultured with DENV-2. IL-18 and ferritin contents in blood, and IL-18 in culture supernatants were determined by ELISA. Increased levels of ferritin and IL-18 (p < 0.0001) were observed in dengue patients, not associated to NS1expression or type of infection (primary or secondary). Highest values of both molecules (p < 0.001) were observed in dengue with warning signs and severe dengue. Differential effect on IL-18/ferritin production was observed associated to viral serotype infection. There were no correlations between ferritin vs. IL-18 production, ferritin vs. NS1 status, and IL-18 vs. NS1 status. Viral-infected monocyte cultures showed increased production of IL-18 (p < 0.001). In conclusion, increased circulating ferritin and IL-18 are expressed in children infected by different serotypes of DENV associated with dengue severity.

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