Conflict of interest: none declared.
Experimental dermatology •Original article
Mycophenolate mofetil and daclizumab targeting T lymphocytes in bleomycin-induced experimental scleroderma
Article first published online: 19 DEC 2011
© The Author(s). CED © 2011 British Association of Dermatologists
Clinical and Experimental Dermatology
Volume 37, Issue 1, pages 48–54, January 2012
How to Cite
Ozgen, M., Koca, S. S., Dagli, A. F., Gundogdu, B., Ustundag, B. and Isik, A. (2012), Mycophenolate mofetil and daclizumab targeting T lymphocytes in bleomycin-induced experimental scleroderma. Clinical and Experimental Dermatology, 37: 48–54. doi: 10.1111/j.1365-2230.2011.04201.x
- Issue published online: 19 DEC 2011
- Article first published online: 19 DEC 2011
- Accepted for publication 26 June 2011
Background. T lymphocytes induce the transformation of fibroblasts into myofibroblasts, the main mediators of fibrogenesis. The inosine 5′-monophosphate dehydrogenase inhibitor mycophenolate mofetil (MMF) and the anti-CD25 monoclonal antibody daclizumab (DCZ) have been reported to suppress the proliferation of T lymphocytes.
Aim. To evaluate the preventive effects of MMF and DCZ in early stages of bleomycin (BLM)-induced scleroderma.
Methods. This study involved five groups of Balb/c mice (n = 10 per group). Mice in four of the groups were injected subcutaneously (SC) with BLM [100 μg/day in 100 μL phosphate-buffered saline (PBS)] for 4 weeks; the remaining (control) group received only 100 μL PBS. Three of the BLM-treated groups also received either intraperitoneal MMF 50 or 150 mg/kg/day, or SC DCZ 100 μg/week. At the end of the fourth week, all mice were killed, and blood and tissue samples were obtained for further analysis.
Results. In the BLM-treated group, increases were seen in inflammatory-cell infiltration, α-smooth muscle actin-positive (α-SMA+) fibroblastic cell count, tissue hydroxyproline content, and dermal thickness. Dermal fibrosis was histopathologically prominent. In BLM-treated mice also given MMF or DCZ, inflammatory-cell infiltration, tissue hydroxyproline content and dermal thickness were decreased. In the MMF groups, decreases were also noted in α-SMA+ fibroblastic cell count.
Conclusion. In this BLM-induced dermal fibrosis model, MMF and DCZ treatments prevented the development of dermal fibrosis. Further studies are needed to evaluate whether targeting T lymphocytes is effective in resolving pre-existing fibrosis in human scleroderma.