Endothelial injury and acute-phase inflammatory mediators converge to drive dengue severity

Severe dengue infection is characterized by endothelial injury and systemic inflammatory complications. To better understand the mechanisms underlying disease severity, we investigated a broad panel of circulating inflammatory and endothelial mediators in patients with clinical dengue infection.

A prospective cross-sectional study was carried out involving 111 dengue patients and 42 healthy controls. Among the dengue cases, 85 were identified as primary, while 26 were classified as secondary dengue infections. Serum levels of endothelial markers (Ang-2, CXCL10, MCP1, and TRAIL), liver dysfunction and acute-phase markers (CRP, galectin 3, and serum amyloid protein), systemic inflammatory mediators (MIF, TNF-α, IL-1β), mast cell-derived proteases (chymase, tryptase), and tissue repair markers HGF, IL-10, IL-1Ra) were quantified using ELISA and Luminex multiplex assays. Correlations among serum analytes, severity indicators, and haematological markers were also explored.

Several biomarkers, Ang-2, CXCL10, TRAIL, CRP, MIF, IL-1Ra, TNF-α, and chymase showed differential expression across severity groups, indicating coordinated endothelial and inflammatory activation. Stratification of patients with primary-secondary dengue also followed a similar pattern except IL-1β, which had significant differential expression across the cohorts. Ang-2 showed strong positive correlations with markers of hepatic dysfunction, including ALT, AST, and bilirubin, suggesting a link between endothelial injury and liver involvement.

Severe dengue is driven by the coordinated activation of endothelial dysfunction, acute-phase responses, mast cell mediators, and counter-regulatory pathways. These processes collectively contribute to vascular leakage and organ injury, reinforcing the value of biomarkers such as Ang-2, CXCL10, CRP, and chymase for severity assessment.