title: The association of cytokines with severe dengue in children.
abstract: BACKGROUND
  Dengue virus infection is a major public health problem. A hypothesis put forward for severe dengue is the cytokine storm, a sudden increase in cytokines that induces vascular permeability. Previous studies and our recent meta-analysis showed that IL-6, IL-8, IFNγ, TNFα, VEGF-A and VCAM-1 are associated with dengue shock syndrome. Therefore, in this study we aim to validate the association of these cytokines with severe dengue.
  
  
  RESULTS
  In a hospital based-case control study in Vietnam, children with dengue fever, other febrile illness and healthy controls were recruited. Dengue virus infection was confirmed by several diagnostic tests. Multiplex immunoassay using Luminex technology was used to measure cytokines simultaneously. A positive association with dengue shock syndrome was found for VCAM-1, whereas a negative association was found for IFNγ. Furthermore, multivariate logistic analysis also showed that VCAM-1 and IFNγ were independently correlated with dengue shock syndrome.
  
  
  CONCLUSIONS
  IFNγ and VCAM-1 were associated with dengue shock syndrome, although their role in the severe dengue pathogenesis remains unclear. Additional studies are required to shed further light on the function of these cytokines in severe dengue.
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University , 1-12-4 Sakamoto, Nagasaki 852-8523, Japan ; Leiden University Medical Center , C-2-R, P.O. Box 9600, 2300 RC Leiden, the Netherlands.
authors.forename: Julia N A
authors.initials: JN
authors.lastname: Mangione
authors.affiliation: Department of Clinical Product Development, Institute of Tropical Medicine (NEKKEN), Nagasaki University , 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Nguyen Tien
authors.initials: NT
authors.lastname: Huy
authors.affiliation: Department of Immunology & Microbiology, Pasteur Institute in Ho Chi Minh City , 167 Pasteur Street, Ho Chi Minh City 70000, Vietnam.
authors.forename: Nguyen Thi Phuong
authors.initials: NT
authors.lastname: Lan
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University , 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Evaristus Chibunna
authors.initials: EC
authors.lastname: Mbanefo
authors.affiliation: Laboratory of Arbovirus, Pasteur Institute in Ho Chi Minh City , 167 Pasteur Street, Ho Chi Minh City 70000, Vietnam.
authors.forename: Tran Thi Ngoc
authors.initials: TT
authors.lastname: Ha
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University , 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Lam Quoc
authors.initials: LQ
authors.lastname: Bao
authors.affiliation: Center for Preventive Medicine , 24 Hung Vuong Street, Vinh Long, Ho Chi Minh City 89000, Vietnam.
authors.forename: Cao Thi Phi
authors.initials: CT
authors.lastname: Nga
authors.affiliation: Center for Preventive Medicine , 24 Hung Vuong Street, Vinh Long, Ho Chi Minh City 89000, Vietnam.
authors.forename: Vo Van
authors.initials: VV
authors.lastname: Tuong
authors.affiliation: Center for Preventive Medicine , 24 Hung Vuong Street, Vinh Long, Ho Chi Minh City 89000, Vietnam.
authors.forename: Tran Van
authors.initials: TV
authors.lastname: Dat
authors.affiliation: Children's Hospital No.2 , 14 Ly Tu Trong street, Ho Chi Minh City 70000, Vietnam.
authors.forename: Tran Thi
authors.initials: TT
authors.lastname: Thuy
authors.affiliation: Children's Hospital No.2 , 14 Ly Tu Trong street, Ho Chi Minh City 70000, Vietnam.
authors.forename: Ha Manh
authors.initials: HM
authors.lastname: Tuan
authors.affiliation: Laboratory of Arbovirus, Pasteur Institute in Ho Chi Minh City , 167 Pasteur Street, Ho Chi Minh City 70000, Vietnam.
authors.forename: Vu Thi Que
authors.initials: VT
authors.lastname: Huong
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University , 1-12-4 Sakamoto, Nagasaki 852-8523, Japan ; Program for Leading Graduate Schools, Nagasaki University , 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirayama
keywords: Association; cytokine; dengue; severity; shock