Infection of peripheral blood mononuclear cells by Herpes Simplex and Epstein-Barr viruses: differential induction of interleukin-6 and tumor necrosis factor

Infection by herpesviruses can result in profound immunosup-pressive or immunomodulatory effects. However, no significant information is available on the effect of such infections on the production of immunoregulatory cytokines. We studied the ki-netics of production of two monocyte-derived cytokines, inter-leukin 6 (IL-6) and tumor necrosis factor-a (TNFa), induced by Epstein-Barr virus (EBV) and herpes simplex virus type 1 (HSV-1) in peripheral blood mononuclear cell cultures and in fractionated cell populations. We observed that, when com-pared to HSV-1, EBV is a stronger inducer of IL-6. In EBV-in-fected cultures, IL-6 protein was detected at day 1 postinfection and gradually increased with time. In contrast, lower amounts of IL-6 were detected 5 d postinfection in HSV-1-infected cul-tures. HSV-1-infected cultures secreted significant amounts of TNFa protein after 5 d of culture and reached a maximal level of production at day 7, whereas EBV inhibited TNFa produc-tion. In fractionated cell populations, monocytic cells were found to be the main source of IL-6 synthesis after EBV or HSV-1 infection. However, TNFa synthesis in HSV-1-in-fected cultures was from both B and monocytic cells. By using the polymerase chain reaction technique we show that, after infection by these two herpesviruses, differences in cytokine gene products are also observed at the transcriptional level. These observations demonstrate that EBV and HSV-1 exert differential effects on IL-6 and TNFa gene transcription and on the resulting protein secretion in human mononuclear bloo