The IL-12 response to herpes simplex virus is mainly a paracrine response of reactive inflammatory cells.

Herpes simplex virus (HSV) infection results in rapid and sustained up-regulation of interleukin (IL)-12, but the primary cellular source of IL-12 after HSV infection is unknown. We demonstrate that this cytokine largely derives from inflammatory cells rather than from productively infected epithelial cells. For optimal IL-12 induction, epithelial cells needed to be infected with replication-competent virus, and cells needed to be able to synthesize proteins. Our results also indicate that HSV-infected cells generate intermediary products that signal recruited inflammatory cells, which themselves were not HSV-infected, to generate IL-12. Possible mechanisms by which infected cells communicate with inflammatory cells to cause IL-12 production are discussed.