Cimetidine has been shown to improve various types of human
neoplasms and more recently it has been shown to be effective in treating recalcitrant or multiple viral
warts in some reports. However, it is not well understood why
cimetidine is effective on those kinds of viral
warts. We investigated 55 patients with multiple viral
warts treated only with oral
cimetidine for up to 4 months to examine the efficacy of treatment. The patients were divided into two groups: group A received oral
cimetidine (<20 mg/kg/day) and group B received the
drug (30 to 40 mg/kg/day). In addition, using real time PCR, we measured
mRNA levels of the
cytokines interleukin-2 (IL-2),
IL-18, and
interferon (IFN)-gamma taken from selected punch biopsy specimens before and during treatment. As a result, 34.5% (19/55) of the patients had a dramatic clinical improvement or complete remission (CR) of their viral
warts and 23.6% (13/55) of the patients had partial responses (PR) within 4 months of
cimetidine therapy.
IL-2 and IFN-gamma
mRNA levels were significantly increased and
IL-18 mRNA levels were decreased in tissues of effectively treated viral
warts. Our results show that the higher dose of oral
cimetidine was more effective in treating multiple viral
warts, that
cimetidine activates Th1 cells to produce
IL-2 and IFN-c and that their expression correlates with
wart remission. These results suggest that
cimetidine is an effective treatment for viral
warts. In addition, based on the decrease in
IL-18 mRNA elicited by the
drug,
IL-18 might be expressed by keratinocytes infected with HPV.