An in vitro model for dengue virus infection that exhibits human monocyte infection, multiple cytokine production and dexamethasone immunomodulation

Abstract

Submitted by Sandra Infurna ([email protected]) on 2019-10-29T13:54:10Z No. of bitstreams: 1 SoniaReginaReis_ClaireKubelka_etal_IOC_2007.pdf: 437848 bytes, checksum: ca87862913a9d9890f95ad406d58b0e8 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-10-29T14:02:20Z (GMT) No. of bitstreams: 1 SoniaReginaReis_ClaireKubelka_etal_IOC_2007.pdf: 437848 bytes, checksum: ca87862913a9d9890f95ad406d58b0e8 (MD5)Made available in DSpace on 2019-10-29T14:02:20Z (GMT). No. of bitstreams: 1 SoniaReginaReis_ClaireKubelka_etal_IOC_2007.pdf: 437848 bytes, checksum: ca87862913a9d9890f95ad406d58b0e8 (MD5) Previous issue date: 2007Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Farmanguinhos. Departamento de Farmacologia Aplicada. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Farmanguinhos. Departamento de Farmacologia Aplicada. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil.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