Efficacy of Kakkon-to, a Traditional Herb Medicine, in Herpes Simplex Virus Type 1 Infection in Mice

Kakkon-to is one of the representative traditional herb medicines (Kampo formulae) and has been used historically for the treatment of infectious diseases in China and Japan. The efficacy of this preparation was characterised using a cutaneous herpes simplex virus type 1 (HSV-1) infection in mice as a model for human viral infection. Kakkon-to at a dose corresponding to human use reduced significantly the mortality of HSV-1-infected mice and localised skin lesions. Delayed type hypersensitivity (DTH) response to HSV-1 antigen was significantly stronger in treated mice than in untreated mice. However, no histopathological difference was noted in the skin lesions between treated and untreated mice except for the size of the lesions. Kakkon-to did not inhibit the growth of HSV-1 in vitro. Natural killer cell activity, natural cytotoxic killer cell activity, and the population of T-cell subsets in spleen cells of infected mice were not affected by the drug. Kakkon-to did not augment interferon induction and anti-HSV-1 antibody production, nor increased cytokine levels such as interleukin-1 alpha, interleukin-2, interferon-gamma, and tumour necrosis factor-alpha in sera of infected mice. Thus, Kakkon-to induced strong DTH to HSV-1 in infected mice, which may have caused localisation of skin lesions and reduction in the mortality of treated mice.