The role of interleukin (IL)-2 and IL-4 in herpes simplex virus type 1 ocular replication and eye disease.

To assess the relative effect of interleukin (IL)-2- and IL-4-dependent immune responses on herpes simplex virus (HSV)-1 infection, naive, vaccinated, and mock-vaccinated IL-20/0 and IL-40/0 knockout mice were challenged ocularly with HSV-1. Naive IL-20/0 mice were significantly more susceptible to lethal infection than IL-40/0 or parental BALB/c mice. Vaccinated, IL-20/0, IL-40/0, and BALB/c mice induced similar neutralizing antibody titers and were completely protected against HSV-1-induced death and corneal scarring. Vaccinated and mock-vaccinated IL-20/0 mice had significantly higher HSV-1 titers in their eyes than BALB/c mice, while vaccinated and mock-vaccinated IL-40/0 mice had significantly lower HSV-1 titers in their eyes than BALB/c mice. Recombinant (r) IL-2 treatment of the IL-20/0 mice significantly reduced ocular HSV-1 replications, but rIL-4 treatment of IL-40/0 mice significantly increased ocular HSV-1 replications. Th1 (IL-2) cytokine responses may help protect mice against ocular HSV-1 challenge and reduce ocular HSV-1 replication.