Increased effects of topically applied interferon on herpes simplex virus-induced lesions by caffeine

Caffeine (Cf, 0.15-0.6 mg/ml) and human leukocyte interferon (IFN, > 5 x 10(2) IU/ml) partially inhibited the replication of herpes simplex virus type 1 (HSV-1) in human diploid LEP cells and HaCaT cells. When the two drugs were applied simultaneously the inhibitory effects exceeded those achieved with either substance alone. In the subsequent clinical trial, which was conducted as a one-center, randomised, and placebo-controlled study, the same substances included in either ointment or solution were used for topical treatment of recurrent herpetic lesions. Of 115 patients taken into the study 20 were treated with Cf only (50 mg/g of ointment or solution), 25 with IFN only (5 x 10(4) IU/g), 25 with mixture of Cf and IFN (same concentrations) and 45 with placebo. Both the healing time (HT, period between the prodromes and reepithelization) and the spreading time (ST, period between the prodromes and the appearance of the last new lesion) were recorded in each patient. While the placebo effects were negligible, the other treatments tended to abort the lesions. HT was shortened by at least 4 days in 75% of patients treated with Cf alone, in 88% of those treated with IFN alone, and in all patients treated with their mixture. The effects on ST were less marked; in the case of Cf alone they were negligible. A shortening of ST by at least 2 days was recorded in 40% and 60% of patients treated with IFN alone and the drug mixture, respectively. Statistical analysis confirmed that both in terms of HT and ST the disease was more significantly alleviated by the mixture of Cf and IFN than by either drug alone.