Interferon‐gamma (IFN‐γ) regulates production of IL‐10 and IL‐12 in human herpesvirus‐6 (HHV‐6)‐infected monocyte/macrophage lineage

To determine whether HHV‐6 infection induces expression and production of IL‐10 and IL‐12 in monocytes/macrophages, and to explore the influence of IFN‐γ on cytokine production in HHV‐6‐infected cells, expression and production of IL‐10 and IL‐12 were evaluated through reverse transcription‐polymerase chain reaction (RT‐PCR) and sandwich ELISA. HHV‐6 infection induced the expression and the production of IL‐10 and IL‐12 in monocytes and THP‐1 cells. Kinetic study showed that the expression of IL‐12 mRNA decreased with accumulation of IL‐10 mRNA. Expression and production of IL‐12 were markedly increased when anti‐human IL‐10 MoAbs were added to the cultures, implying that endogenous IL‐10 induced by HHV‐6 inhibited IL‐12 production. Addition of increasing concentrations of IFN‐γ to the cultures of HHV‐6‐infected cells enhanced the expression of IL‐12 gene, while the accumulation of IL‐10 mRNA was down‐regulated. Determination of protein levels of IL‐10 and IL‐12 by ELISA also showed that IFN‐γ increased IL‐12 and decreased IL‐10 production. These results suggest that IFN‐γ regulates the production of IL‐10 and IL‐12 at transcriptional level mainly through inhibiting endogenous IL‐10 production in HHV‐6‐infected monocyte/macrophage lineage.