Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity.
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-1beta, IFN-gamma, 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-1beta levels were observed in patients with mild dengue. MIP-1beta was also associated with CD56+NK cell circulating rates. IL-1beta, IL-8, TNF-alpha and MCP-1 were associated with marked thrombocytopenia. Increased MCP-1 and GM-CSF levels correlated with hypotension. Moreover, MIP-1beta and IFN-gamma were independently associated with both dengue severity and disease outcome.


CONCLUSIONS
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-beta is indicated for the first time as a good prognostic marker in contrast to IFN-gamma that was associated with disease severity.
Bozza
Fernando A
FA
Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. fernando.bozza@ipec.fiocruz.br
Cruz
Oswaldo G
OG
Zagne
Sonia M O
SM
Azeredo
Elzinandes L
EL
Nogueira
Rita M R
RM
Assis
Edson F
EF
Bozza
Patricia T
PT
Kubelka
Claire F
CF
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001938:Brazil; D054407:Chemokine CCL4 / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D003715:Dengue / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007371:Interferon-gamma / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012720:Severity of Illness Index
D015415:Biomarkers; C066507:CCL4 protein, human; D054407:Chemokine CCL4; D016207:Cytokines; D007371:Interferon-gamma