Which cytokine is primarily responsible for the increased vascular permeability and plasma leakage observed in dengue hemorrhagic fever (DHF) in children?

Explanation

## Pathophysiology of Dengue Hemorrhagic Fever **Key Point:** TNF-α is the primary mediator of vascular permeability and plasma leakage in DHF. It acts on endothelial cells to increase intercellular junction permeability, leading to the characteristic plasma extravasation. **High-Yield:** The pathogenesis of DHF involves a cytokine storm dominated by TNF-α, along with IL-2, IL-6, and IL-8. This occurs particularly during secondary dengue infection due to antibody-dependent enhancement (ADE). ### Mechanism of Plasma Leakage | Cytokine | Role in DHF | Effect on Endothelium | |----------|-------------|----------------------| | TNF-α | Primary mediator | Increased permeability, tight junction disruption | | IL-6 | Amplification of inflammation | Systemic inflammatory response | | IL-8 | Neutrophil recruitment | Endothelial damage | | IL-10 | Anti-inflammatory | Downregulates TNF-α (not primary cause) | **Clinical Pearl:** The critical phase of dengue (days 3–7 of illness) coincides with defervescence and peak TNF-α levels, not viremia. This paradoxical worsening after fever subsidence is a hallmark of DHF and is driven by TNF-α–mediated endothelial dysfunction. **Mnemonic:** **PLASMA LEAK = TNF-α PEAK** — Remember that TNF-α peaks during defervescence and causes the dangerous plasma leakage phase in DHF.