Role of interleukin-18 in peripheral blood mononuclear cells infected withhuman herpes virus type 6

Objective: Interleukin 18 (IL-18) production represents a critical step in the polarization of the Th1 immune response. Human herpes virus type 6 (HHV -6) possesses a peculiar tropism for immunocompetent cells. To understand t he relationships among immunocompetent cells, HHV-6 and cytokines, the role of IL-18 during infection of peripheral blood mononuclear cells (PBMC) wit h HHV-6 was evaluated. Methods: PBMC were obtained from healthy HHV-6-seron egative donors, after centrifugation of heparinized venous blood over a Fic oll-Hypaque gradient. Supernatants from PBMC were analyzed for the presence of cytokines. To study the effects of exogenous recombinant human (rh) IL- 18 on HHV-6 replication, the number of cells expressing viral antigens and the amount of extracellular virus were analysed. Results: No basal producti on of IL-18 was found in supernatants of unstimulated PBMC. Appreciable amo unts of the cytokine were produced by lipopolysaccharicle (LPS)-stimulated PBMC. HHV-6 infection of LPS-treated PBMC downregulated IL-18 production. I t was found that the addition of rhIL-18 to HHV-6-infected PBMC downregulat ed the percentage of antigen-positive cells and the release of extracellula r virus. Conclusion: Impairment of IL-18 release, which is involved in the induction of antiviral cytokines, such as interferon-y, could represent a s trategy of the virus to evade the immune response of the host. Copyright (C ) 2001 S. Karger AG, Basel.