Protection of burn mice infected with herpesviruses by benzoylmesaconine (BEN) combined with IL-12

The majority of death in thermally injured patients is associated with infection. Herpesviruses have been identified as typical viral pathogens in bum patients. In the present study the effect of BEN combined with IL-12 treatments on the infection of herpes simplex virus type 1 (HSV) in thermally injured mice (TI-mice) was examined, because TI-mice become susceptible to the HSV infection based upon generating burn -associated CD8⁺ type 2 T cells which are influenced by these two substances in different mechanisms. BALB/c mice, subjected to a flame burn (3rd degree, 30% of total body surface area), were challenged i.p. with HSV (KOS strain). BEN, a non-toxic alkaloid extracted from Aconiti tuber, was supplied from Tsumura & Co., Tokyo, Japan. IL-12 was kindly provided from Genetics Institute, Cambridge, MA, and Hoffmann-La Roche, Inc., Nutley, NJ. TI-mice infected with HSV (4 × 10³ PFU/kg) were treated orally with 0.1 μg/kg of BEN and/or 500 U/mouse of IL-12 i.p. IL-12 protected TI-mice infected with a lethal dose of HSV it was administered to mice before the infection. Mortalities in 80%, 90% or 90% of TI-mice infected with HSV were shown when they were treated with IL-12, BEN or saline (0.2 ml/mouse) one and 3 days after the infection, respectively. However, 80% of TI-mice survived when they were treated therapeutically in a combination with BEN and IL-12. These results suggest that synergistic antiviral effects are produced in TI-mice infected with HSV by a combined administration of BEN and IL-12.