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