Nephrol Dial Transplant (2003) 18: 878-883
© 2003 European Renal Association-European Dialysis and Transplant Association
Modulation of autoantibody production by mycophenolate mofetil: effects on the development of SLE in (NZBxNZW)F1 mice
1 Servicio de Nefrología and 2 Unidad de Investigación, Hospital Universitario Marqués de Valdecilla and 3 Departamento de Ciencias Médicas y Quirúrgicas and 4 Departamento de Fisiología y Farmacología, Universidad de Cantabria, Santander, Spain
Background. Mycophenolate mofetil (MMF) has been successfully used to improve or prevent the development of systemic lupus erythematosus (SLE) in both humans and in several lupus-prone mice. In the present study, we evaluated mechanisms through which MMF may exert its therapeutic effect on the development of systemic autoimmunity.
Methods. (NZBxNZW)F1 female mice were continuously treated with 100 mg/kg/day (high dose) or 30 mg/kg/day (low dose) MMF beginning at 3 months of age. The development of an autoimmune syndrome was evaluated by measuring immunoglobulin (Ig) isotypes of autoantibodies and their levels, as well as by evaluating immunopathological kidney abnormalities and mortality curves.
Results. At both doses, MMF efficiently modulated the development of SLE. Although the higher dose of MMF directly inhibited the production of autoantibodies, 30 mg/kg/day MMF promoted qualitative but not quantitative changes in autoantibodies in (NZBxNZW)F1 female mice. These qualitative changes were manifested as a selective reduction in total or antigen-specific IgG2a antibody levels.
Conclusions. The mechanisms through which MMF controls the development of SLE in (NZBxNZW)F1 females is highly dependent upon immunosuppressor dose. Interestingly, lower dose MMF selectively reduced IgG2a antibody levels, suggesting that this dose may modulate TH1 CD4+ activity.
Keywords: autoantibodies; mycophenolate mofetil; (NZBxNZW)F1 mice; systemic lupus erythematosus
Correspondence and offprint requests to: Dr Ramón Merino, Unidad de Investigación, Hospital Universitario Marqués de Valdecilla, Escuela de Enfermería 4 planta, Av. Valdecilla s/n, E-39008 Santander, Spain. Email: merinor{at}unican.es
The authors wish it to be known that, in their opinion, the last two authors contributed equally to this work and share senior authorship.
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