Dinamic changes of pro-inflammatory cytokines, adhesion molecules and lymphocytes activation markers as early indicators of diseases severity in patients with Dengue

Abstract

Several immunopathogenic mechanisms have been proposed to explain the massive increase of vascular permeability observed in the severe forms of infection by Dengue Virus (DENV). Our aim was to determine the kinetic changes of inflammatory mediators (IL-8, TNF- α), soluble early lymphocyte activation markers (sIL-2R, sTNF-Rp75) and soluble fractions of cell adhesion molecules (sICAM-1 and sVCAM-1) as indicators for early recognition of disease severity in patients with laboratory-confirmed dengue. Twenty patients classified as Dengue±Warning Signs (D±WS) and thirty patients with Severe Dengue (SD) were included in the study. Serums of apparently healthy individuals were included as controls. Compared with normal subjects, D±WS cases did not show significant differences in the levels of IL-8 or TNF-α during the acute nor in the critical stages of the disease; however, in D±WS cases levels of sICAM-1 and sVCAM-1 were higher than controls during both phases; in contrast, significant increase of sTNF-p75 and sIL2R levels were observed during the critical phase of the disease. Compared with both dengue patients and controls, patients with SD showed significant rise in the levels of IL-8 and TNF-α during the critical phase of the disease and a significant increase in adhesion molecules were detected in both phases, but the highest levels of sVCAM-1 and sIL-2R were observed only during the acute stage of the disease. In conclusion, sIL-2R and sVCAM-1, as early markers of lymphocyte and endothelial activation, would serves as indicators of severity during the acute phase of dengue infection.

Keywords

• Dengue
• cytokines
• endothelial damage
• soluble cell adhesion molecules
• soluble lymphocyte markers
• citoquinas
• disfunción endotelial
• moléculas de adhesión células solubles
• marcadores solubles linfociticos