Cutaneous
fungal infections are frequently associated with an inflammatory component including irritated skin,
itching and stinging/burning. Therapeutic
anti-fungal agents that have anti-inflammatory activity have the potential to provide clinical benefit beyond fungus eradication. Recently, certain
anti-fungal agents have been shown to have intrinsic anti-inflammatory activity, therefore we sought to determine the extent of the anti-inflammatory activity of these compounds. The anti-inflammatory activities of eight
anti-fungal agents (
butoconazole,
ciclopirox olamine,
fluconazole,
miconazole nitrate,
sertaconazole nitrate,
terconazole,
tioconazole and
ketoconazole) were compared in a number of preclinical models of dermal
inflammation and
pruritus. While
butoconazole,
ciclopirox olamine,
fluconazole, and
miconazole nitrate were all found to have anti-inflammatory activity, only
sertaconazole nitrate reduced the release of
cytokines from activated lymphocytes and mitigated
inflammation in animal models of
irritant contact dermatitis and
neurogenic inflammation. In addition,
sertaconazole nitrate inhibited
contact hypersensitivity and scratching responses in a murine model of
pruritus. Furthermore, the in vitro and in vivo anti-inflammatory activity of
sertaconazole nitrate was found to be greater than other topical
anti-fungal agents examined. These studies demonstrate that
topical administration of clinically relevant concentrations of
sertaconazole nitrate resulted in an efficacious anti-inflammatory activity against a broad spectrum of dermal
inflammation models and itch. The anti-inflammatory properties of
sertaconazole may contribute to the efficacy of the
drug in the treatment of cutaneous fungal conditions and provide greater anti-inflammatory activity compared with other
anti-fungal agents.