Mycophenolate mofetil and daclizumab targeting T lymphocytes in bleomycin-induced experimental scleroderma.
Clin Exp Dermatol
; 37(1): 48-54, 2012 Jan.
Article
en En
| MEDLINE
| ID: mdl-22182434
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Esclerodermia Localizada
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Inmunoglobulina G
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Anticuerpos Monoclonales Humanizados
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Inmunosupresores
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Ácido Micofenólico
Límite:
Animals
Idioma:
En
Revista:
Clin Exp Dermatol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Turquía