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Dengue Patients with Early Hemorrhagic Manifestations Lose Coordinate Expression of the Anti-Inflammatory Cytokine IL-10 with the Inflammatory Cytokines IL-6 and IL-8

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  • 1 Divisão de Epidemiologia e Controle de Doenças/Instituto Octávio Magalhães, Fundação Ezequiel Dias, Belo Horizonte, Minas Gerais, Brazil.
  • | 2 Divisão de Plataformas Tecnológicas/Diretoria de Pesquisa e Desenvolvimento, Fundação Ezequiel Dias, Belo Horizonte, Minas Gerais, Brazil.
  • | 3 Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
  • | 4 Programa de Pós-graduação em Medicina e Biomedicina, Instituto de Ensino e Pesquisa, Hospital Santa Casa, Belo Horizonte, Minas Gerais, Brazil.
  • | 5 Institutos Nacionais de Ciências e Tecnologia-Doenças Tropicais, Belo Horizonte, Minas Gerais, Brazil.
  • | 6 Núcleo de Ensino e Pesquisa, Instituto Mario Penna, Belo Horizonte, Minas Gerais, Brazil.
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Dengue is responsible for a wide range of clinical manifestations, ranging from asymptomatic infections to severe cases. The alteration of cytokine levels correlated with clinical characteristics can help determine prognostic markers of the disease and the identification of targets for immunotherapy. We measured the viral load, serotype, and cytokine levels of 212 serum samples from patients with acute dengue infection during days 1–4 after the onset of symptoms. The patients were classified as either with hemorrhagic manifestations (HM) or with no hemorrhagic manifestations (NHM). The cytokines interleukin-6 (IL-6), IL-8, and IL-10 were increased (P < 0.05) in the dengue virus+ group, compared with the control group. A higher viral load (P < 0.05) and IL-6 was detected in the HM group compared with the NHM group. Interestingly, the NHM group demonstrated a significant positive correlation between inflammatory (IL-6 and 8) and anti-inflammatory (IL-10) cytokines, whereas the HM group did not. These findings suggest that a disturbance in the balance of inflammatory cytokines IL-6 and IL-8 with the anti-inflammatory cytokine, IL-10, combined with the high levels of IL-6 and viral load, characterize possible mechanisms related to the formation of HM.

Author Notes

* Address correspondence to Kenneth J. Gollob, Núcleo de Ensino e Pesquisa, Instituto Mario Penna, R. Joaquim Cândido Filho, 1420, Belo Horizonte, Minas Gerais 30380-420 Brazil. E-mail: kjgollob@gmail.com

Financial support: This work was supported by the Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), the Fundação Ezequiel Dias (FUNED), Instituto Mario Penna, and CNPq, INCT-DT/CNPq.

Authors' addresses: Felipe Campos de Melo Iani, Myrian Morato Duarte, and Ana Luisa Furtado Cury, Divisão de Epidemiologia e Controle de Doenças/Instituto Octávio Magalhães (IOM), Fundação Ezequiel Dias (FUNED), Belo Horizonte, Brazil, E-mails: felipe.iani@funed.mg.gov.br, myrian.duarte@funed.mg.gov.br, and ana.cury@funed.mg.gov.br. Sérgio Caldas and Alzira Batista Cecílio, Divisão de Plataformas Tecnológicas/Diretoria de Pesquisa e Desenvolvimento, Fundação Ezequiel Dias (FUNED), Belo Horizonte, Brazil, E-mails: sergio.caldas@funed.mg.gov.br and alzira.cecilio@funed.mg.gov.br. Pedro Augusto Carvalho Costa and Lis R. Antonelli, Centro de Pesquisas René Rachou (CPqRR), Fundação Oswaldo Cruz (FIOCRUZ), Belo Horizonte, Brazil, E-mails: costa@cpqrr.fiocruz.br and lisantonelli@cpqrr.fiocruz.br. Kenneth J. Gollob, Instituto de Ensino e Pesquisa, Hospital Santa Casa; Institutos Nacionais de Ciências e Tecnologia-Doenças Tropicais; Núcleo de Ensino e Pesquisa, Instituto Mario Penna, Belo Horizonte, Minas Gerais, Brazil, Belo Horizonte, Minas Gerais, Brazil, E-mail: kjgollob@gmail.com.

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