| | Cytokines | Biological function | Refs. |
| | MCP-1 | Monocyte chemoattractant protein-1 is critical to drive the extravasation of mononuclear cells into the inflamed, infected, and traumatized sites of infection. In addition, it promotes endothelial permeability increasing the vascular leakage as a result of dengue virus infection. | [47, 48] |
| | IL-1 | It induces tissue factor (TF) expression of endothelial cells (EC) and suppresses their cell surface anticoagulant activity. It may upregulate TNF-α production and activity. IL-1β mediates platelet-induced activation of ECs, which increases chemokine release and upregulates VCAM-1 enhancing adhesion of monocytes to the endothelium. | [43, 49] |
| | IL-6 | It has been described as a strong inducer of endothelial permeability resulting in vascular leakage. IL-6 potentiates the coagulation cascade and can downregulate production of TNF-α and its receptors. IL-6 may perform a synergistic role with some pyrogens such as IL-1 to induce fever. | [50, 51] |
| | IL-8 | Its systemic concentrations are increased by EC damage, which in turn induces endothelial permeability. Activation of the coagulation system results in increased expression of IL-6 and IL-8 by monocytes, while the APC anticoagulation pathway downregulates the production of IL-8 by ECs. | [49, 50, 52] |
| | IL-10 | It plays an immunosuppressive role that causes IFN resistance, followed by impaired immune clearance and a persistent infectious effect for acute viral infection. IL-10 also inhibits the expression of TF and inhibits fibrinolysis. IL-10 plasma levels have been associated with disease severity; however, its role in dengue pathogenesis has not been fully elucidated. | [53] |
| | TNF-α | It is a potent activator of ECs; it enhances capillary permeability. TNF-α upregulates expression of TF in monocytes and ECs and downregulates expression of thrombomodulin on ECs. It also activates the fibrinolytic system and enhances expression of NO mediating activation-induced death of T cells, and it has therefore been implicated in peripheral T-cell deletion. | [49, 51, 54] |
| | TGF-β | Early in infection, low levels of TGF-β may trigger secretion of IL-1 and TNF-β. However, later in infection, the cytokine inhibits the Th1 response and enhances production of Th2 cytokines such as IL-10. TGF-β increases expression of TF on ECs and upregulates expression and release of PAI-1 (plasminogen activator inhibitor-1). | [3] |
| | VEGF | VEGF is a key driver of vascular permeability. It reduces EC occludins, claudins, and the VE-cadherin content, all of which are components of ECs junctions. Upon activation, VEGF stimulates expression of ICAM-1, VCAM-1, and E-selectin in ECs. | [3, 36] |
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