Cambios dinámicos de citoquinas proinflamatorias, moléculas de adhesión y marcadores de activación linfocítica como indicadores tempranos de severidad en pacientes con Dengue

Varios mecanismos inmuno-patogenicos se han propuesto para explicar el incremento masivo de la permeabilidad vascularobservada en las formas severas de la infeccion por el Virus del Dengue (DENV). El objetivo del estudio fue determinar loscambios cineticos de mediadores inflamatorios (IL-8, TNF-α), marcadores soluble de activacion linfocitica temprana (sIL-2R,sTNF-Rp75) y fracciones solubles de moleculas de adhesion celular (sICAM-1, sVCAM-1) como marcadores tempranos deseveridad en pacientes con dengue. Veinte pacientes clasificados como Dengue (Dengue±Signos de Alarma,D±WS) y treintapacientes con Dengue Severo (DS) fueron incluidos en el estudio. Suero de individuos aparentemente saludables fueronincluidos como controles. En comparacion con los individuos controles, los casos con Dengue mostraron niveles de IL-8 yTNF con diferencias no significativas en la fase febril o critica de la enfermedad; sin embargo, un incremento significativo desICAM-1 y sVCAM-1 ocurrio en ambas fases, mientras que los niveles de sIL2R y sTNF-p75 se elevaron significativamentesolo en la fase critica de la enfermedad. En comparacion con los casos con dengue y controles, los pacientes con DS mostraron diferencias significativas en los niveles de IL-8 y TNF-α durante la fase critica y un incremento significativo demoleculas de adhesion en ambas fases, pero los niveles mas elevados de sVCAM-1 y sIL-2R fueron observados en la fasefebril. En conclusion, sIL-2R y sVCAM-1, como marcadores tempranos de activacion linfocitica y endotelial, servirian comoindicadores de severidad en la fase aguda de la infeccion por el virus del dengue. Dinamic changes of pro-inflammatory cytokines, adhesion molecules and lymphocytesactivation 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 permeabilityobserved in the severe forms of infection by Dengue Virus (DENV). Our aim was to determine the kinetic changes ofinflammatory mediators (IL-8, TNF- α), soluble early lymphocyte activation markers (sIL-2R, sTNF-Rp75) and solublefractions of cell adhesion molecules (sICAM-1 and sVCAM-1) as indicators for early recognition of disease severity inpatients with laboratory-confirmed dengue. Twenty patients classified as Dengue±Warning Signs (D±WS) and thirty patientswith 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 theacute nor in the critical stages of the disease; however, in D±WS cases levels of sICAM-1 and sVCAM-1 were higher thancontrols during both phases; in contrast, significant increase of sTNF-p75 and sIL2R levels were observed during the criticalphase of the disease. Compared with both dengue patients and controls, patients with SD showed significant rise in thelevels of IL-8 and TNF-α during the critical phase of the disease and a significant increase in adhesion molecules weredetected in both phases, but the highest levels of sVCAM-1 and sIL-2R were observed only during the acute stage of thedisease. In conclusion, sIL-2R and sVCAM-1, as early markers of lymphocyte and endothelial activation, would serves asindicators of severity during the acute phase of dengue infection.