Research article

Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity

Fernando A Bozza¹ , Oswaldo G Cruz² , Sonia MO Zagne³ , Elzinandes L Azeredo⁴ , Rita MR Nogueira⁵ , Edson F Assis⁶ , Patricia T Bozza⁶ and Claire F Kubelka⁴

¹  Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

²  Programa de Computação Científica, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

³  Hospital Universitário Antonio Pedro, Universidade Federal Fluminense, Niterói, Brazil

⁴  Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

⁵  Laboratório de Flavivirus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

⁶  Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

author email corresponding author email

BMC Infectious Diseases 2008, 8:86doi:10.1186/1471-2334-8-86

Published:	25 June 2008

Abstract

Background

Dengue virus pathogenesis is not yet fully understood and the identification of patients at high risk for developing severe disease forms is still a great challenge in dengue patient care. During the present study, we evaluated prospectively the potential of cytokines present in plasma from patients with dengue in stratifying disease severity.

Methods

Seventeen-cytokine multiplex fluorescent microbead immunoassay was used for the simultaneous detection in 59 dengue patients. GLM models using bimodal or Gaussian family were determined in order to associate cytokines with clinical manifestations and laboratory diagnosis.

Results

IL-1β, IFN-γ, IL-4, IL-6, IL-13, IL-7 and GM-CSF were significantly increased in patients with severe clinical manifestations (severe dengue) when compared to mild disease forms (mild dengue). In contrast, increased MIP-1β levels were observed in patients with mild dengue. MIP-1β was also associated with CD56+NK cell circulating rates. IL-1β, IL-8, TNF-α and MCP-1 were associated with marked thrombocytopenia. Increased MCP-1 and GM-CSF levels correlated with hypotension. Moreover, MIP-1β and IFN-γ were independently associated with both dengue severity and disease outcome.

Conclusion

Our data demonstrated that the use of a multiple cytokine assay platform was suitable for identifying distinct cytokine profiles associated with the dengue clinical manifestations and severity. MIP-β is indicated for the first time as a good prognostic marker in contrast to IFN-γ that was associated with disease severity.