The effect of danazol in the MRL/lpr mouse model of autoimmune disease.
The purpose of the study was to determine if danazol was efficacious in the treatment of lupus MRL/MpJ (lpr) mice, as measured by longevity, proteinuria and serum amyloid protein (SAP) levels. Danazol, administered at an oral dose of 100 mg/kg, significantly prolonged survival of female MRL/MpJ (lpr) mice but had no effect on the mortality of their male counterparts. Medication with danazol began 40 days after birth of the mice and resulted in a significant decrease in proteinuria in female but not male lupus mice. The concentration of SAP, an acute phase reactant, was significantly decreased in danazol-treated female lupus mice at 80, 100, 120, 140 and 160 days of age when compared to vehicle-treated control mice. SAP levels in male lupus mice treated with danazol were significantly lower than normal control levels only at the 120 and 160 day time points. Measurements of mortality, proteinuria and SAP concentration indicate that danazol at 100 mg/kg is orally active in the treatment of MRL/MpJ (lpr) female, but not male mice.
Connolly
K M
KM
Department of Chemotherapy, Glaxo Inc., Research Triangle Park, North Carolina 27709.
Stecher
V J
VJ
Snyder
B W
BW
Bohnet
E
E
Potts
G O
GO
D000682:Amyloid / Q000097:blood; D000818:Animals; D001327:Autoimmune Diseases / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D003613:Danazol / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000235:genetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011245:Pregnadienes / Q000627:therapeutic use*; D011507:Proteinuria / Q000188:drug therapy; D012737:Sex Factors
D000682:Amyloid; D011245:Pregnadienes; D003613:Danazol