The Association of Cytokines with Severe Dengue in Children

Abstract

Background: Dengue virus infection is a major public health problem. A hypothesis put forward for severe dengue is the cytokine storm, a sudden increase in cytokines that induces vascular permeability. Previous studies and our recent meta-analysis showed that IL-6, IL-8, IFNγ, TNFα, VEGF-A and VCAM-1 are associated with dengue shock syndrome. Therefore, in this study we aim to validate the association of these cytokines with severe dengue. Methods & Findings: In a hospital based-case control study in Vietnam, children with dengue fever, other febrile illness and healthy controls were recruited. Dengue virus infection was confirmed by several diagnostic tests. Multiplex immunoassay using Luminex technology was used to measure cytokines simultaneously. A positive association with dengue shock syndrome was found for VCAM-1, whereas a negative association was found for IFNγ. Furthermore, multivariate logistic analysis also showed that VCAM-1 and IFNγ were independently correlated with dengue shock syndrome. Conclusion: IFNγ and VCAM-1 were associated with dengue shock syndrome, although their role in the severe dengue pathogenesis remains unclear. Additional studies are required to shed further light on the function of these cytokines in severe dengue.

Biomarkers in differentiating clinical dengue cases: A prospective cohort study

“…As opposed to previous study, VCAM-1 could not differentiate among the different severity of dengue cases in our study [34]. Other studies were conducted in children indicated VCAM-1 could differentiate the different severity of dengue cases [17,35,36].…”

Interleukin-6: A promising disease severity index for dengue virus infection

“…Our data showed that IL-6 expression level in DHF patients was significantly higher than that in DF patients and healthy controls, which is completely in agreement with the findings of other report [20]. A number of clinical studies demonstrated higher level of pro-inflammatory cytokines most importantly IL-6 in sera from either DF or DHF patients in comparison with healthy subjects [21][22][23][24].…”

The correlation of TNF alpha levels with the lipid profile of dengue patients

“…1 TNF-α is a key pro-inflammatory cytokine that has been associated with many biological functions such as lipid metabolism 11 ; it is well known that DF and DHF patients have significantly higher levels of pro-inflammatory cytokines. 12,13 In the present study, we found increased levels of cholesterol and LDL in HBD compared with dengue patients, whereas cholesterol, LDL, and HDL levels were significantly lower in DHF than in DF and/or HBD. Furthermore, we found higher levels of TNF-α in DF patients compared to HBD.…”

“…Lipid metabolism is extensively regulated by cytokines during the host response to infection . TNF‐α is a key pro‐inflammatory cytokine that has been associated with many biological functions such as lipid metabolism; it is well known that DF and DHF patients have significantly higher levels of pro‐inflammatory cytokines …”