Human monocyte-mediated cytotoxicity against herpes simplex virus-infected cells: activation of cytotoxic monocytes by free and liposome-encapsulated lymphokines.

Human peripheral blood monocytes were incubated with free or liposome-encapsulated human lymphokines containing macrophage-activating factor (MAF) and tested for their effect on herpes simplex virus (HSV)-infected target cells. Activated monocytes lysed allogeneic HSV type 2 (HSV-2)-infected whole human embryo cells and xenogeneic BALB/c mouse embryo cells (10E2) without any significant effect on uninfected cells, as measured by release of 51Cr from target cells after 18 h of cocultivation. Kinetic studies revealed that lysis of virus-infected cells occurred by 10 h following cocultivation with activated monocytes. The inability of free MAF or supernatants from MAF-activated monocytes to lyse HSV-2-infected cells suggested that direct monocyte-target cell contact is required for monocyte-mediated cytotoxicity of the virus-infected cells. Monocytes activated with MAF suppressed the production of HSV-2 and HSV-1 from virus-infected cells more than control monocytes did. In addition, monocytes treated with liposome-encapsulated MAF selectively destroyed HSV-2-infected cells but left uninfected cells unharmed. The capacity of liposome-encapsulated immunomodulators to activate human monocytes to selectively lyse HSV-2-infected cells has potential therapeutic benefit and should be evaluated in vivo.