Elevated serum levels of high mobility group box 1 (HMGB1) protein in dengue-infected patients are associated with disease symptoms and secondary infection

Background: Dengue virus (DENV) is described as the most prevalent arbovirus, infecting at least 50 million people worldwide. During infection, an intricate network of cytokines, a group of substances closely related to disease severity, is released. Recently, it was observed that both DENV-infected epithelial cells undergoing necrosis and dendritic cells (DCs) are able to release a non-classical pro-inflammatory cytokine called high mobility group box 1 (HMGB1). Objectives: The aim of this study was to evaluate whether HMGB1 levels were altered in DENV-infected patients' sera and whether this augment correlated with disease pathogenesis. Study design: Samples from DENV-infected patients were collected from different days after the onset of symptoms and from patients experiencing primary or secondary infection. The circulating HMGB1 concentration was measured in healthy blood donors as well as in donors with primary and secondary cases of DENV infection by a quantitative capture ELISA assay. Results: We observed that the HMGB1 concentration in DENV-infected patients was significantly higher than in healthy patients. HMGB1 levels reached the highest concentration in the first day after the onset of symptoms and decreased throughout the course of the infection. Moreover, we observed that the HMGB1 concentration was augmented during secondary infection as well. Conclusion: We hypothesize that HMGB1 levels correlate with disease pathogenesis, specifically with the clinical symptoms and secondary infection, implicating a pro-inflammatory cytokine role for HMGB1 in DENV infection. This is the first report assessing the circulating levels of HMGB1 during DENV infection. (C) 2012 Published by Elsevier B.V.