Infection of murine keratinocytes with herpes simplex virus type 1 induces the expression of interleukin-10, but not interleukin-1 alpha or tumour necrosis factor-alpha.

Herpes simplex virus (HSV) is known to possess several mechanisms whereby it can evade the normal host immune defences. In this study the expression of the immunosuppressive cytokine, interleukin (IL)-10, was monitored following infection of a murine keratinocyte cell line (PAM-212) and compared with the expression of two proinflammatory cytokines: IL-1 alpha and tumour necrosis factor (TNF)-alpha. The PAM-212 cells were infected at a multiplicity of 0.5 with a clinical isolate of HSV type 1, and the mRNA of the three cytokines was assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) over the following 24 hr. By 12 hr postinfection the amount of IL-10 mRNA had increased significantly to five-fold greater than that found in uninfected cells (P < 0.01), and this elevated level was maintained until at least 24 hr postinfection. In contrast, IL-1 alpha and TNF-alpha mRNAs were not significantly up-regulated by the HSV infection. Immunostaining with an IL-10 monoclonal antibody (mAb) revealed that cytoplasmic IL-10 protein had increased by 6-12 hr postinfection. This quantity was further increased at 24 hr postinfection, when the viral cytopathic effect was apparent. Viral replication was necessary, but not sufficient on its own, for IL-10 induction. Experiments with HSV mutants lacking functional transactivating factors suggested that the viral transactivating proteins ICP-0 and VP-16 may be necessary for HSV-induced IL-10 expression. Thus, the up-regulation in the expression of IL-10 mRNA and protein induced by HSV early in the infection of keratinocytes represents a specific response and may be part of the viral strategy to avoid local immune defence mechanisms in the skin.