Local hyperthermia could induce antiviral activity by endogenous interferon-dependent pathway in condyloma acuminata

Abstract

Local hyperthermia has been successfully used in the treatment of viral warts by mechanisms that have largely remained unclear. Using an organotypic culture system, we found that hyperthermia at 42 °C and 45 °C could induce a significant increase in the transcriptional expression of interferon (IFN)-α, IFN-β and IFN-γ, in a temperature-dependent manner in condyloma acuminata (CA), but not in normal skin. Accordingly, local hyperthermia could enhance the expression of 2'-5' oligoadenylate synthase and double-stranded RNA (dsRNA)-dependent protein kinase, two antiviral enzymes downstream of the IFN-dependant pathway. Hyperthermia led to an increase in IFN-α/β receptor transcripts, and an increase in the levels in phospho-Stat1 and phospho-Stat2 in CA, though it had no influence on the levels of Jak1, Tyk2, Stat1 and Stat2 transcriptional expression. Local hyperthermia was proved effective in treating human papillomavirus-infected skin. These results suggested that hyperthermia took effect partly by inducing the expression of local endogenous IFN and partly by subsequent IFN-induced antiviral activity via Jak-STATs signalling pathway in CA.