Immunosuppressive effects of gemcitabine in the HSV-induced Behçet's disease like mouse model

Objective

To study effects and side effects of gemcitabine (2',2'-difluorodeoxycytidine, dFdC), a pyrimidine synthesis inhibitor, on skin lesions of a herpes simplex virus-induced Behçet's disease (BD)-like mouse model.

Methods

Dose-escalation studies with dFdC were performed in ICR mice with intraperitoneal application over 5 days. After inoculation of ICR mice with herpes simplex virus and classification as having BD according to a revised Japanese classification, 18 BD-mice were randomly assigned to placebo, 0.06 or 0.12 μg of dFdC/day over 5 days. Serum levels of interleukin (IL)-4, IL-6, IL-10, tumor necrosis factor-α and interferon-γ were determined using ELISA assays.

Results

After application of 3 μg dFdC over 5 days, alanine aminotransferase increased (P = 0.032) but all other kidney and liver parameters were unchanged. In BD mice, 5 days of dFdC treatment with 0.06 or 0.12 μg of dFdC/day resulted in a dose-dependent improvement in 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.

Conclusion

DFdC shows promising effects to improve cutaneous lesions in the herpes simplex virus-induced BD-like mouse model. In this animal model, effects of dFdC on the cytokine profile remained inconclusive.