Primary dengue virus infections induce differential cytokine production in Mexican patients

Abstract

Severe dengue pathogenesis is not fully understood, but high levels of proinflammatory cytokines have been associated with dengue disease severity. In this study, the cytokine levels in 171 sera from Mexican patients with primary dengue fever (DF) and dengue haemorrhagic fever (DHF) from dengue virus (DENV) 1 (n = 116) or 2 (n = 55) were compared. DF and DHF were defined according to the patient’s clinical condition, the primary infections as indicated by IgG enzymatic immunoassay negative results, and the infecting serotype as assessed by real-time reverse transcription-polymerase chain reaction. Samples were analysed for circulating levels of interleukin (IL)-12p70, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, IL-6, and IL-8 using a commercial cytometric bead array. Significantly higher IFN-γ levels were found in patients with DHF than those with DF. However, significantly higher IL-12p70, TNF-α, and IL-6 levels were associated with DHF only in patients who were infected with DENV2 but not with DENV1. Moreover, patients with DF who were infected with DENV1 showed higher levels of IL-12p70, TNF-α, and IL-6 than patients with DHF early after-fever onset. The IL-8 levels were similar in all cases regardless of the clinical condition or infection serotype. These results suggest that the association between high proinflammatory cytokine levels and dengue disease severity does not always stand, and it once again highlights the complex nature of DHF pathogenesis.

Meta-analysis of biomarkers for severe dengue infections

“…Fifty-six studies were included in this meta-analysis. The authors of forty-nine studies were contacted for unpublished data, and two sets of authors, Eppy et al (2016) and De la Cruz Hernández et al (2016) , responded to provide their unpublished data. These two studies were also included.…”

“…In vitro studies have found no structural damage or cell death in infected endothelial cells ( Chaturvedi et al, 2000 ; Srikiatkhachorn et al, 2006 ). Moreover, differences in levels of cytokines and chemokines were found when sera/plasma samples from dengue hemorrhagic fever (DHF) and dengue fever (DF) patients were compared ( De la Cruz Hernández et al, 2016 ), which suggests that severe symptoms are caused by the cytokines and chemokines that act as mediators and vasodilators in blood, rather than by direct virus-induced cell damage. This hypothesis also explains the observation that severe symptoms occur during defervescence, after the decrease of viremia ( Dejnirattisai et al, 2008 ).…”

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

“…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 …”

Identifying protein biomarkers in predicting disease severity of dengue virus infection using immune-related protein microarray

“…[ 4 ] The phenomena of original antigenic sin, [ 6 ] immune evasion that inhibits interferon (IFN)-α and IFN-β signaling by suppressing Jak-Stat activation, [ 7 ] a cytokine storm, [ 8 ] and autoimmune responses [ 9 ] are thought to contribute to the pathogenesis of severe form of dengue disease. However, contradictory findings have been proposed by Hernández et al, [ 10 ] where no significant association was observed between the level of proinflammatory cytokines and disease severity, reflecting the complex nature of pathophysiology of dengue disease.…”