Role of interleukin-18 in peripheral blood mononuclear cells infected with human 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 the relationships among immunocompetent cells, HHV-6 and cytokines, the role of IL-18 during infection of peripheral blood mononuclear cells (PBMC) with HHV-6 was evaluated.


METHODS
PBMC were obtained from healthy HHV-6-seronegative donors, after centrifugation of heparinized venous blood over a Ficoll-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 production of IL-18 was found in supernatants of unstimulated PBMC. Appreciable amounts of the cytokine were produced by lipopolysaccharide (LPS)-stimulated PBMC. HHV-6 infection of LPS-treated PBMC downregulated IL-18 production. It was found that the addition of rhIL-18 to HHV-6-infected PBMC downregulated the percentage of antigen-positive cells and the release of extracellular virus.


CONCLUSIONS
Impairment of IL-18 release, which is involved in the induction of antiviral cytokines, such as interferon-gamma, could represent a strategy of the virus to evade the immune response of the host.
Arena
A
A
Institute of Medical Microbiology, Policlinico Universitario, University of Messina, Via C. Valeria, I-98125 Messina, Italy.
Iannello
D
D
Gazzara
D
D
Speranza
A
A
Bonina
L
L
Mastroeni
P
P
D002478:Cells, Cultured; D015654:Herpesvirus 6, Human / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D020382:Interleukin-18 / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D008070:Lipopolysaccharides / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation; D014779:Virus Replication
D020382:Interleukin-18; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D007371:Interferon-gamma