title: Serum-dependent enhancement of coxsackievirus B4-induced production of IFNα, IL-6 and TNFα by peripheral blood mononuclear cells.
abstract: Only a few reports have been published on the interactions between Coxsackievirus B4 (CVB4) and human peripheral blood mononuclear cells (PBMC) but have not been extensively documented. Human serum containing non-neutralizing anti-CVB4 antibodies increased CVB4-induced synthesis of IFNα by PBMC. In this study, we determined if CVB4 and human serum have the ability to activate inflammatory cytokines in addition to IFNα in PBMC cultures. PBMC from healthy donors were inoculated with infectious, inactivated CVB4 or with CVB4 incubated with dilutions of human serum or polyvalent IgG with anti-CVB4 activity. Levels of IFNα, TNFα, IL-6, IL-12, IFNγ and IL-10 in the cell-free supernatants of PBMC cultures were measured using ELISA. Infection was assessed by real-time PCR. PBMC inoculated with CVB4 produced inflammatory cytokines but not IFNα. When CVB4 was incubated with serum or IgG, IFNα was detected in the culture supernatants, and high concentrations of TNFα and IL-6 were measured. The concentrations of TNFα and IL-6 were not reduced in cultures inoculated with inactivated CVB4, whereas the IgG-dependent enhancement of IFNα, IL-6 and TNFα production with inactivated virus was suppressed. The potentiation of IFNα production was associated with a high intracellular viral load. Infectious and non-infectious CVB4 can induce the production of inflammatory cytokines but not IFNα by PBMC. High levels of IFNα, in addition to TNFα and IL-6, in culture supernatants were obtained when infectious CVB4 was combined with immune serum or IgG, and they were associated with high amounts of intracellular viral RNA.
authors.affiliation: Université Lille 2, Faculté de Médecine, CHRU, Laboratoire de Virologie EA3610, Loos-lez-Lille 59120, France.
authors.forename: Enagnon Kazali
authors.initials: EK
authors.lastname: Alidjinou
authors.forename: Famara
authors.initials: F
authors.lastname: Sané
authors.forename: Ilka
authors.initials: I
authors.lastname: Engelmann
authors.forename: Didier
authors.initials: D
authors.lastname: Hober
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology*; D002478:Cells, Cultured; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D029822:Enterovirus B, Human / Q000276:immunology* / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007106:Immune Sera / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000821:virology; D008070:Lipopolysaccharides / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000737:chemistry; D012367:RNA, Viral / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D038301:Virus Inactivation
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; C508600:IL6 protein, human; D007106:Immune Sera; D007074:Immunoglobulin G; D016898:Interferon-alpha; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha
keywords: Enterovirus; FCS; RT-PCR; T1D; cytokines; fetal calf serum; immunoglobulin G; in vitro; inflammation; real-time PCR; type 1 diabetes