Dactinomycin treatment of murine lupus erythematosus. I. Renal disease and longevity

• Published in: Laboratory investigation Vol. 39; no. 5; pp. 441 - 448
• Main Authors: Rudofsky, U H, Urizar, R E, Gabrielsen, A E, Simmons, A D, Olsen, C T
• Format: Journal Article
• Language: English
• Published: United States 01.11.1978
• Subjects: Animals; Antigen-Antibody Complex; Dactinomycin - therapeutic use; Disease Models, Animal; Fluorescent Antibody Technique; Glomerulonephritis - drug therapy; Glomerulonephritis - mortality; Glomerulonephritis - pathology; Immune Complex Diseases - drug therapy; Immune Complex Diseases - mortality; Immune Complex Diseases - pathology; Lupus Erythematosus, Systemic - drug therapy; Lupus Erythematosus, Systemic - mortality; Lupus Erythematosus, Systemic - pathology; Mice; Microscopy, Electron
• ISSN: 0023-6837

Three groups of female (NZB X NZW)F1 hybrid mice were treated with an intermittent regimen of dactinomycin (actinomycin D), 3.5 microgram. daily. Median survival was doubled in two of the groups and increased by more than 75 per cent in the third. Most of the treated animals never had significant proteinuria. When kidneys from 14 treated mice, which died between the ages of 11 and 20 months, were examined by light and fluorescence microscopy, most showed the lesions of normal aged CBA and C57BL/6 mice, some expansion of the mesangial matrix and increased cellularity, consistent with deposition of immunoglobulins and complement components in the mesangium, generally sparing the capillary loops. Four of the 14 animals, three of them long-lived, had advanced renal glomerular disease. These data indicate that dactinomycin, by whatever therapeutic mechanism, permits very extended survival of B/W female mice, the large majority of them without significant renal disease.