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Therapeutic effects of gemcitabine on cutaneous manifestations in an Adamantiades–Behçet's disease‐like mouse model
Author(s) -
Sohn Seonghyang,
Lutz Manfred,
Kwon Hyuk Jae,
Konwalinka Guenther,
Lee Sungnack,
Schirmer Michael
Publication year - 2004
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.0906-6705.2004.00210.x
Subject(s) - gemcitabine , medicine , cytokine , antimetabolite , pharmacology , tumor necrosis factor alpha , ganciclovir , immunology , endocrinology , chemotherapy , virus , human cytomegalovirus
The aim of this work was to study the effects and side effects of gemcitabine (2′,2′‐difluorodeoxycytidine, dFdC), a pyrimidine synthesis inhibitor, on skin lesions of a herpes simplex virus (HSV)‐induced Adamantiades–Behçet's disease (ABD)‐like mouse model. For the dose‐escalation study, ICR mice were treated intraperitoneally with dFdC over 5 days. For the efficacy study, ICR mice were inoculated with HSV and classified as having ABD according to a revised Japanese classification, and then 18 ABD mice were randomly assigned to placebo, 0.06 or 0.12 µg of dFdC/day over 5 days. Serum levels of interleukin‐4 (IL‐4), IL‐6, IL‐10, interferon‐γ (IFN‐γ), and tumor necrosis factor‐α (TNF‐α) were determined using enzyme‐linked immunosorbent assay. After application of 3 µg of dFdC over 5 days, alanine aminotransferase increased ( P = 0.032), but all other kidney and liver parameters were unchanged. In ABD mice, 5 days of dFdC treatment with 0.06 or 0.12 µg of dFdC/day resulted in a dose‐dependent improvement of cutaneous manifestations by more than 60% ( P = 0.017). There was no significant change in cytokine levels, and none of the cytokine levels correlated with response to treatment. Moreover, dFdC shows promising effects to improve cutaneous lesions in the HSV‐induced ABD‐like mouse model. In this animal model, effects of dFdC on the cytokine profile remained inconclusive.