Early Immune Activation in Acute Dengue Illness Is Related to Development of Plasma Leakage and Disease Severity

TLDR

T lymphocyte activation and elevated cytokine levels are known to occur in children with dengue hemorrhagic fever. Serial plasma samples were collected from Thai children within 72 h of fever onset to assess immune markers. Children who progressed to DHF exhibited higher plasma concentrations of sTNFR80, soluble CD8, IL‑2 receptor, IFN‑γ, sTNFR60, and TNF‑α than those with dengue fever or other febrile illnesses, and these elevations correlated with plasma leakage, indicating that immune activation contributes to DHF pathogenesis. Further studies are needed to evaluate the predictive value of sTNFR80 for DHF.

Abstract

T lymphocyte activation and increased cytokine levels have been described in retrospective studies of children presenting with dengue hemorrhagic fever (DHF). Serial plasma samples obtained in a prospective study of Thai children presenting with <72 h of fever were studied. Plasma levels of 80-kDa soluble tumor necrosis factor receptors (sTNFRs) were higher in children who developed DHF than in those with dengue fever (DF) or other nondengue febrile illnesses (OFIs) and were correlated with the degree of subsequent plasma leakage. Soluble CD8 and soluble interleukin-2 receptor levels were also elevated in children with DHF compared with those with DF. Interferon-gamma and sTNFR 60-kDa levels were higher in children with dengue than in those with OFIs. TNF-alpha was detectable more often in DHF than in DF or OFIs (P<.05). These results support the hypothesis that immune activation contributes to the pathogenesis of DHF. Further studies evaluating the predictive value of sTNFR80 for DHF are warranted.