An in vitro model for dengue virus infection that exhibits human monocyte infection, multiple cytokine production and dexamethasone immunomodulation.
An important cytokine role in dengue fever pathogenesis has been described. These molecules can be associated with haemorrhagic manifestations, coagulation disorders, hypotension and shock, all symptoms implicated in vascular permeability and disease worsening conditions. Several immunological diseases have been treated by cytokine modulation and dexamethasone is utilized clinically to treat pathologies with inflammatory and autoimmune etiologies. We established an in vitro model with human monocytes infected by dengue virus-2 for evaluating immunomodulatory and antiviral activities of potential pharmaceutical products. Flow cytometry analysis demonstrated significant dengue antigen detection in target cells two days after infection. TNF-alpha, IFN-alpha, IL-6 and IL-10 are produced by in vitro infected monocytes and are significantly detected in cell culture supernatants by multiplex microbead immunoassay. Dexamethasone action was tested for the first time for its modulation in dengue infection, presenting optimistic results in both decreasing cell infection rates and inhibiting TNF-alpha, IFN-alpha and IL-10 production. This model is proposed for novel drug trials yet to be applied for dengue fever.
Reis
Sônia Regina Nogueira Ignácio
SR
Laboratório de Imunologia Viral, Instituto Oswaldo Cruz-Fiocruz, 21040-900 Rio de Janeiro, RJ, Brasil.
Sampaio
André Luiz Franco
AL
Henriques
Maria das Graças Muller
Md
Gandini
Mariana
M
Azeredo
Elzinandes Leal
EL
Kubelka
Claire Fernandes
CF
D000956:Antigens, Viral / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects*; D003716:Dengue Virus / Q000187:drug effects* / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007155:Immunologic Factors / Q000494:pharmacology*; D016898:Interferon-alpha / Q000096:biosynthesis / Q000187:drug effects; D007378:Interleukins / Q000096:biosynthesis; D009000:Monocytes / Q000276:immunology / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
D000956:Antigens, Viral; D016207:Cytokines; D005938:Glucocorticoids; D007155:Immunologic Factors; D016898:Interferon-alpha; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone