Altered cytokine production after human herpes virus type 6 infection.
Several strategies allow viruses to elude the surveillance of the immune system and to establish persistent infection in the host. One of such mechanisms 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 CD8+ T cells, B cells, monocytes/macrophages, megakaryocytes and NK cells. In this study the production of IL-10 and IL-12 by peripheral blood mononuclear cells (PBMC) was evaluated during HHV-6 infection "in vitro". Our results demonstrate that HHV-6 up-regulates IL-10 production by PBMC. Furthermore, our data suggest that rhIFN gamma addition counteracts the effect of HHV-6 in promoting IL-10 release. To gain more insight into the role of IFN gamma, anti-IFN gamma monoclonal antibodies were added to PBMC stimulated with LPS. Neutralization of endogenous IFN gamma upregulated IL-10 release. Furthermore, HHV-6 infection inhibited IFN gamma release induced by LPS in PBMC. No basal production of IL-12 was found in PBMC. Moreover, HHV-6 infection did not induce IL-12 release by PBMC. On the contrary, IL-12 was detected in the supernatants of PBMC treated with LPS with or without rhIFN gamma. In these experimental conditions the further addition of HHV-6 markedly impaired IL-12 production. Moreover, the neutralization of IL-10 resulted in a significant up-regulation of IL-12. Finally our data suggest that the immunodysregulation induced by HHV-6 could be accounted for by a shift from a Th-1 to a Th-2 type cytokine profile.
Arena
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A
Institute of Medical Microbiology, Policlinico Universitario University of Messina, Italy.
Liberto
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MC
Iannello
D
D
Capozza
A B
AB
Focà
A
A
D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D015654:Herpesvirus 6, Human / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000821:virology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D011994:Recombinant Proteins; D015854:Up-Regulation
D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D016753:Interleukin-10; D007371:Interferon-gamma