A Combination Therapy Using IL-12 and Soluble IL-4 Receptor on Herpes Simplex Virus Type 1 Infection in a Human–SCID Chimera Model of Thermal Injury

Herpes simplex virus type 1 (HSV-1) is a severe pathogen in thermally injured patients. Type 1 T cells are essential for the hostʹs anti-HSV protective immunity. Type 2 cytokines, commonly detected in thermally injured patients, have been described as inhibitors for the type 1 T cell generation. Therefore, the antiviral effects of combination therapy with a type 1 T cell inducer [interleukin (IL)-12] and a type 2 T cell inhibitor [soluble IL-4 receptor (sIL-4R)] were investigated in severe combined immunodeficiency (SCID) mice inoculated with peripheral blood lymphocytes (PBL) of thermally injured patients. Patient PBL–SCID chimeras (SCID mice inoculated with patient PBL) were susceptible to infection with 1 × 103 PFU/kg of HSV-1 (0% survival), while healthy PBL–SCID chimeras (SCID mice inoculated with PBL from healthy donors) were resistant (92% survival). When patient PBL–SCID chimeras exposed to HSV-1 were treated with saline, human recombinant (r) IL-12 or human sIL-4R, 0, 0, or 12.5% of them survived, respectively. However, 75% of these chimeras survived when they were treated with rIL-12 and sIL-4R in combination. These results indicate that HSV-1 infection in patient PBL–SCID chimeras was therapeutically controlled by the inducer of type 1 T cell responses and the inhibitor of type 2 T cell responses in combination.