Transgenic expression of interleukin-6 in the central nervous system confers protection against acute herpes simplex virus type-1 infection

IL-6 is a pro-inflammatory cytokine that has previously been associated wit h herpes simplex virus type 1 reactivation. To further investigate this rel ationship during acute infection, ocular HSV-1 infection was studied in tra nsgenic mice homozygous or heterozygous expression of IL-6 by astrocytes in the central nervous system. The virus load in both the eye and trigeminal ganglia was significantly reduced at day 6 but not day 3 post infection in the homozygous IL-6 transgenic mice compared to the wild type and heterozyg ous littermates. IL-6 protein and mRNA levels in the eye coincided with the level of transgene expression in mice acutely infected with virus (i.e., d ay 3 post infection). Likewise, IL-6 transcript levels in the TG mirrored t he expression of the transgene in the mice throughout the course of the inf ection into latency. The HSV-1 alpha lytic phase gene ICP27 was rapidly dow n-regulated by day 6 post infection in the TG of homozygous IL-6 transgenic mice compared to the wild type and heterozygous littermates. The resistanc e to acute HSV-1 infection in the homozygous IL-6 transgenic mice correlate d with a significant elevation in IFN-alpha/beta in the eye compared to the wild type or heterozygous IL-6 transgenic animals. Heterozygous and homozy gous IL-6 transgenic mice latently infected with HSV-1 showed elevated anti -HSV-1 antibody titers compared to the latently infected wild type controls . Collectively, the results suggest dose-dependent IL-6 antagonism of acute HSV-1 infection in vivo.