TNF and dengue disease: The underlying mechanisms driving plasma leakage are not fully understood but are hypothesized to involve multiple pathways: (1) elevated cell-mediated and humoral immune response to dengue disease, especially in cases of dengue reinfection; (2) secretion of pro-inflammatory molecules (including tumor necrosis factor α, interleukin 6, interleukin 8 and platelet activating factor); (3) destruction of the endothelial glycocalyx due to dengue virus non-structural protein-1 (NS1); and (4) formation of excessive reactive oxygen species [59–61].