Enhanced inhibition of herpes simplex virus type 1 growth in human corneal fibroblasts by combinations of interferon-alpha and -gamma.

Trials testing the topical treatment of herpes simplex virus (HSV) ocular infections with single interferons (IFN) have provided mixed results. To determine if combination therapy with IFN may be more effective, the ability of combinations of IFN-alpha and IFN-gamma to inhibit HSV growth in human corneal fibroblasts (HCF) was assessed. Virus yields were reduced 282-fold and 37-fold, respectively, in HCF treated with either IFN-alpha or IFN-gamma (10(3) units/mL each). In cells treated with a combination of IFN-alpha and IFN-gamma (10(3) units/mL each), an average reduction of 5.1 x 10(5)-fold in the yield of infectious virus was achieved. Combinations of IFN-alpha and IFN-gamma considerably enhanced the antiviral effect in HCF, suggesting that combination treatment may be efficacious against ocular HSV infections; these findings provide a possible explanation at the cellular level for the poor results achieved in previous clinical trials.