Infection of murine keratinocytes with herpes simplex virus type 1 inducesthe 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 follo wing infection of a murine keratinocyte cell line(PAM-212) and compared wit h the expression of two proinflammatory cytokines: IL-1 alpha and tumour ne crosis factor (TNF)-alpha. The PAM-212 cells were infected at a multiplicit y of 0.5 with a clinical isolate of HSV type 1, and the mRNA of the three c ytokines was assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) over the following 24 hr. By 12 hr postinfection th e amount of IL-10 mRNA had increased significantly to five-fold greater tha n that found in uninfected cells (P<0.01), and this elevated level was main tained until at least 24 hr postinfection. In contrast, IL-1<alpha> and TNF -alpha mRNAs were not significantly up-regulated by the HSV infection. Immu nostaining with an IL-10 monoclonal antibody (mAb) revealed that cytoplasmi c IL-10 protein had increased by 6-12 hr postinfection. This quantity was f urther increased at 24 hr postinfection, when the viral cytopathic effect w as apparent. Viral replication was necessary, but not sufficient on its own , for IL-10 induction. Experiments with HSV mutants lacking functional tran sactivating 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 b e part of the viral strategy to avoid local immune defence mechanisms in th e skin.