Effect of IL-12 combined with soluble IL-4 receptor in thermally injured mice exposed to large amounts of herpes simplex virus type 1

Thermally injured mice, which mount Th2 responses, exhibit impaired resistance to infection with herpes simplex virus type 1 (HSV-1). Previously we reported that in thermally injured mice infected with HSV-1 at a dose of 5 LD₅₀ (corresponds to 0.05 LD₅₀ in normal mice), therapeutic treatment with IL-12 failed to inhibit the progression of the systemic disease. When EL-12 and soluble IL-4 receptor (sIL-4R) were administered together, they induced a marked recovery in the impaired resistance of thermally injured mice to HSV-1 infection. In the present study, therefore, the effect or a combination therapy between IL-12 and sIL-4R on a severe HSV-1 infection in thermally injured mice was investigated. BALB/c mice were exposed to a flame burn (3rd degree, 30% of total body surface area). Then, they were challenged i.p. with 50 to 500 LD₅₀ of HSV-1 and treated with IL-12 and sIL-4R in combination. IL-12 was kindly provided by Hoffmann-La Roche, Inc., Nutley, NJ. Soluble IL-4 receptor (sIL-4R) was obtained commercially from Genzyme, Cambridge, MA. When thermally injured mice were treated with IL-12 (500 U/mouse, i.p, 2 and 4 days after thermal injury) or sDL-4R (50 μg/mouse, i.p., 1 and 4 days after thermal injury) alone, all of mice died within 13 days after the HSV-1 infection. However, 70% of HSV-1 infected thermally injured mice survived after the combination therapy between IL-12 and sH/-4R. At this time, 0% or 75% of normal mice treated with saline or IL-12 alone survived after the infection, respectively. These results suggest that the therapeutic IL-12 treatment combined with sIL-4R may result in the protection of thermally injured mice exposed to a severe HSV-1 infection.