Altered cytokine production after human herpes virus type 6 infection

Several strategies allow Viruses to elude the surveillance of the immune sy stem and to establish persistent infection in the host. One of such mechani sms is the immunosuppression caused by the direct infection and functional impairment of immune cells. Human Herpes virus type 6 (HHV-6) is a typical immunosuppressive agent, as suggested by its tropism for both CD4(+) and CD 8(+) T cells, B cells, monocytes/macrophages, megakaryocytes and NK cells. In this study the production of IL-10 and IL-12 by peripheral blood mononuc lear cells (PBMC) was evaluated during HHV-6 infection "in vitro". Our resu lts demonstrate that HHV-6 up-regulates IL-10 production by PBMC. Furthermo re, our data suggest that rhIFN gamma addition counteracts the effect of HH V-6 in promoting IL-10 release. To gain more insight into the role of IFN g amma, anti-IFN gamma monoclonal antibodies were added to PBMC stimulated wi th LPS. Neutralization of endogenous IFN gamma upregulated IL-10 release. F urthermore, HHV-6 infection inhibited IFN gamma release induced by LPS in P BMC. No basal production of IL-12 was found in PBMC. Moreover, HHV-6 infect ion did not induce IL-12 release by PBMC. On the contrary, IL-12 was detect ed in the supernatants of PBMC treated with LPS with or without rhIFN gamma . In these experimental conditions the further addition of HHV-6 markedly i mpaired IL-12 production. Moreover, the neutralization of IL-10 resulted in a significant up-regulation of IL-12. Finally our data suggest that the im munodysregulation induced by HHV-6 could be accounted for by a shift from a Th-1 to a Th-2 type cytokine profile.