Alteration of Cytokines and Chemokines During Febrile Episodes Associated With Endothelial Cell Damage and Plasma Leakage in Dengue Hemorrhagic Fever

Background: The leakage of plasma during febrile episodes in dengue-infected patients is a severe condition leading to dengue shock syndrome. Alteration of cytokines/chemokines is suspected to be a major cause of endothelial cell damage in these patients. The study was designed to demonstrate the alteration of cytokines and chemokines in dengue-infected patients during febrile episodes. Methods: The blood samples from 164 patients with dengue fever, dengue hemorrhagic fever and other febrile illnesses were collected daily from the day of hospitalization until discharge and also in the convalescent stage. The levels of cytokines/chemokines were determined using a sandwich chemilu-minescent immunoassay, and the hematological parameters were examined by the ADVIA hematological analyzer. Results: Two patterns of cytokines/chemokines alteration were detected at different time points during the febrile episode. The increased factors included interleukin (IL)-4, IL-6, IL-8, IL-10, tumor necrosis factor-alpha, interferon-gamma and monocyte chemoattractant protein-1 whereas IL-1 beta, IL-2, vascular endothelial growth factor and epidermal growth factor were decreased. Several cytokines were correlated with disease severity especially in dengue hemorrhagic fever/dengue shock syndrome patients. Conclusions: The alteration in the cytokine/chemokine kinetics during a febrile episode can be used as a predictor for severe dengue infection. The increased and decreased levels at different time points can indicate the disease progression related to vascular leakage in dengue hemorrhagic fever/dengue shock syndrome patients.