Résumé
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 IFNa by PBMC. In this study, we determined if CVB4 and human serum have the ability to activate inflammatory cytokines in addition to IFNa 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 IFN alpha, TNF alpha, IL-6, IL-12, IFNy 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 IFN alpha. When CVB4 was incubated with serum or IgG, IFN alpha was detected in the culture supernatants, and high concentrations of TNF alpha and IL-6 were measured. The concentrations of TNFa and IL-6 were not reduced in cultures inoculated with inactivated CVB4, whereas the IgG-dependent enhancement of IFN alpha, IL-6 and TNF alpha production with inactivated virus was suppressed. The potentiation of IFN alpha production was associated with a high intracellular viral load. Infectious and non-infectious CVB4 can induce the production of inflammatory cytokines but not IFNa by PBMC. High levels of IFN alpha, in addition to TNF alpha 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. (C) 2013 Elsevier Ltd. All rights reserved.