Murine chronic graft-versus-host disease as a model of systemic lupus erythematosus: effect of immunosuppressive drugs on disease development.
The effect of a number of drugs commonly used to treat the more severe exacerbations of the autoimmune disease systemic lupus erythematosus (SLE) in humans has been investigated in the murine chronic graft-versus-host (GVH) induced model of lupus. This was undertaken in order to determine the value of this model for the investigation of immunomodulant drugs, with particular regard to the reproducibility of disease induction and methods of monitoring disease progression. The drugs were azathioprine, cyclophosphamide, cyclosporin A and dexamethasone. All of these, except for azathioprine, reduced disease severity, assessed as the development of lupus nephritis. Anti-ssDNA autoantibodies were also reduced in titre in the dexamethasone-treated group. Overall, these findings, combined with the reproducible induction of disease seen in this model, support the use of chronic GVH disease as a model for SLE and show that the induced disease can be ameliorated by drugs effective in the treatment of SLE in humans.
Appleby
P
P
Research Department, Boots Company, Nottingham, England.
Webber
D G
DG
Bowen
J G
JG
D000818:Animals; D001379:Azathioprine / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D003524:Cyclosporins / Q000627:therapeutic use; D003849:Deoxyguanosine; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008181:Lupus Nephritis / Q000517:prevention & control; D051379:Mice; D011507:Proteinuria / Q000517:prevention & control; D015203:Reproducibility of Results
D003524:Cyclosporins; D007166:Immunosuppressive Agents; D003907:Dexamethasone; D003520:Cyclophosphamide; D003849:Deoxyguanosine; D001379:Azathioprine