Antiviral effects of recombinant human tumor necrosis factor-alpha in combination with natural interferon-beta in mice infected with herpes simplex virus type 1

The protective effects of combination therapy utilizing recombinant human TNF-alpha (rTNF-α) and natural murine interferon-beta (IFN-β) in mice infected with herpes simplex virus type 1 (HSV-1) was investigated. Mice treated with rTNF-α alone at all of the doses tested (a single i.v. administration, 2.3-2,300 μg/kg; multiple i.p. administrations 0.4-250 μg/kg) as well as mice that received IFN-β alone at doses of 16 × 10⁴ U/kg or less resulted in a 0% survival rate. Combination therapy consisting of a single administration of rTNF- α (230 and 23 μg/kg) and multiple administrations of IFN-β (4 × 10⁴ U/kg) resulted in a 40% and 60% survival rate. Multiple treatments of infected mice with rTNF-α (50 and 10 μg/kg) in combination with IFN-β (4 × 10⁴ U/kg) resulted in 50% and 70% survival rates, respectively. These results suggest that the combination therapy of rTNF and natural murine IFN-β produce synergistic protective effects in mice infected with a lethal amount of HSV-1.