Background: There is a lack of specific
antiviral therapy against dengue virus (DENV) in current use. Therefore, a great proportion of
dengue cases progress to severe clinical forms due to a complex interplay between virus and host immune response. It has been hypothesized that heterotypic non-
neutralizing antibodies enhance DENV
infection in phagocytic cells, and this induces an inflammatory response that is involved in the pathogenesis of
severe dengue. Purpose: To identify the
antiviral and immunomodulatory effects of
polyphenols on dengue virus
infection. Methods: Human U937-DC-SIGN macrophages were infected with DENV serotypes 2 or 3 in the presence or not of enhancing antibody 4G2. Viral titers and the secretion of
tumor necrosis factor-alpha,
IL-6,
IL-10 and
interferon-alpha were analyzed timely. Results: DENV
infection alone induced high production of
IL-6 and TNF-α, but in the presence of 4G2 antibody, viral titers and TNF-α secretion were potentiated. Based on anti-inflammatory antecedents, the
polyphenols curcumin,
fisetin,
resveratrol,
apigenin,
quercetin and
rutin were tested for
antiviral and immunomodulatory properties. Only
quercetin and
fisetin inhibited DENV-2 and DENV-3
infection in the absence or presence of enhancing antibody (>90%, p<0.001); they also inhibited TNF-α and
IL-6 secretion (p<0.001). Conclusion:
Quercetin and
fisetin down-regulate the production of proinflammatory
cytokines induced by DENV
infection enhanced by
antibodies a mechanism involved in
severe dengue.