title: Primary dengue virus infections induce differential cytokine production in Mexican patients.
abstract: Severe dengue pathogenesis is not fully understood, but high levels of proinflammatory cytokines have been associated with dengue disease severity. In this study, the cytokine levels in 171 sera from Mexican patients with primary dengue fever (DF) and dengue haemorrhagic fever (DHF) from dengue virus (DENV) 1 (n = 116) or 2 (n = 55) were compared. DF and DHF were defined according to the patient's clinical condition, the primary infections as indicated by IgG enzymatic immunoassay negative results, and the infecting serotype as assessed by real-time reverse transcription-polymerase chain reaction. Samples were analysed for circulating levels of interleukin (IL)-12p70, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, IL-6, and IL-8 using a commercial cytometric bead array. Significantly higher IFN-γ levels were found in patients with DHF than those with DF. However, significantly higher IL-12p70, TNF-α, and IL-6 levels were associated with DHF only in patients who were infected with DENV2 but not with DENV1. Moreover, patients with DF who were infected with DENV1 showed higher levels of IL-12p70, TNF-α, and IL-6 than patients with DHF early after-fever onset. The IL-8 levels were similar in all cases regardless of the clinical condition or infection serotype. These results suggest that the association between high proinflammatory cytokine levels and dengue disease severity does not always stand, and it once again highlights the complex nature of DHF pathogenesis.
authors.affiliation: Departamento de Virología, Instituto de Diagnóstico y Referencia Epidemiológicos, México, DF, México.
authors.forename: Sergio Isaac de la
authors.initials: SI
authors.lastname: Cruz Hernández
authors.affiliation: Departamento de Infectómica y Patogénesis Molecular, Instituto Politécnico Nacional, Centro de Investigación y Estudios Avanzados, México, DF, México.
authors.forename: Henry Nelson
authors.initials: HN
authors.lastname: Puerta-Guardo
authors.affiliation: Departamento de Inmunología e Inmunogenética, Instituto de Diagnóstico y Referencia Epidemiológicos, México, DF, México.
authors.forename: Hilario
authors.initials: H
authors.lastname: Flores Aguilar
authors.affiliation: Departamento de Virología, Instituto de Diagnóstico y Referencia Epidemiológicos, México, DF, México.
authors.forename: Silvia
authors.initials: S
authors.lastname: González Mateos
authors.affiliation: Departamento de Virología, Instituto de Diagnóstico y Referencia Epidemiológicos, México, DF, México.
authors.forename: Irma
authors.initials: I
authors.lastname: López Martinez
authors.affiliation: Departamento de Biomedicina, Instituto Politécnico Nacional, Centro de Investigación y de Estudios Avanzados, México, DF, México.
authors.forename: Vianney
authors.initials: V
authors.lastname: Ortiz-Navarrete
authors.affiliation: Departamento de Infectómica y Patogénesis Molecular, Instituto Politécnico Nacional, Centro de Investigación y Estudios Avanzados, México, DF, México.
authors.forename: Juan E
authors.initials: JE
authors.lastname: Ludert
authors.affiliation: Departamento de Infectómica y Patogénesis Molecular, Instituto Politécnico Nacional, Centro de Investigación y Estudios Avanzados, México, DF, México.
authors.forename: Rosa María del
authors.initials: RM
authors.lastname: Angel
mesh_terms: D016207:Cytokines / Q000378:metabolism*; D003715:Dengue / Q000276:immunology; D003716:Dengue Virus / Q000145:classification / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008800:Mexico; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D065288:Serogroup; D019595:Severe Dengue / Q000097:blood / Q000276:immunology*; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma