Treatment of end stage MRL-1pr/lpr mouse lupus disease by a cyclophosphazene derived drug and by cyclosporin A.
MRL-lpr/lpr mice develop T cell lymphadenopathy, polyclonal activation of B lymphocytes, autoantibodies and lupus nephritis. B and T cell populations, the dysfunctions of which play a role in the pathophysiology of the mouse disease, represent potential targets for lupus treatment. MRL-lpr/lpr mice are treated from the age of 19 weeks, i.e. after the onset of renal disease and lymphoproliferation, with Cyclosporin A which acts at the T cell level, or with DIAM4 which can down modulate polyclonal activation of B lymphocytes. DIAM4 induces the disappearance of the lymphoproliferation, the increase in C3 levels and the decrease in anti-DNA antibody, immunoglobulin and urea levels, and proteinuria. Cyclosporin A reduces lymph node hyperplasia, but has no effect on other parameters of the disease.
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Laboratoire d'Immunopathologie Rénale et d'Immunopharmacologie CJF INSERM 88.01, Faculté de Médecine Purpan, Toulouse, France.
Dueymes
M
M
Appolinaire-Pilipenko
S
S
Sournies
F
F
Labarre
J F
JF
Fournié
G J
GJ
D000367:Age Factors; D000419:Albuminuria / Q000188:drug therapy / Q000209:etiology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001388:Aziridines / Q000494:pharmacology / Q000627:therapeutic use*; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use*; D006942:Hypergammaglobulinemia / Q000188:drug therapy / Q000235:genetics; D007136:Immunoglobulins / Q000032:analysis; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D008232:Lymphoproliferative Disorders / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains / Q000276:immunology*; D009943:Organophosphorus Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D012965:Sodium Chloride / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001388:Aziridines; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D009943:Organophosphorus Compounds; D012965:Sodium Chloride; D016572:Cyclosporine; C050390:DIAM 4