title: Mycophenolate mofetil and daclizumab targeting T lymphocytes in bleomycin-induced experimental scleroderma.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of Rheumatology, Faculty of Medicine, Firat University, Elazig, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Ozgen
authors.forename: S S
authors.initials: SS
authors.lastname: Koca
authors.forename: A F
authors.initials: AF
authors.lastname: Dagli
authors.forename: B
authors.initials: B
authors.lastname: Gundogdu
authors.forename: B
authors.initials: B
authors.lastname: Ustundag
authors.forename: A
authors.initials: A
authors.lastname: Isik
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use; D001761:Bleomycin; D016207:Cytokines / Q000378:metabolism; D000077561:Daclizumab; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006909:Hydroxyproline / Q000032:analysis; D007074:Immunoglobulin G / Q000494:pharmacology* / Q000627:therapeutic use; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D012594:Scleroderma, Localized / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012867:Skin / Q000737:chemistry / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D001761:Bleomycin; D000077561:Daclizumab; D009173:Mycophenolic Acid; D006909:Hydroxyproline