Immunosuppressive activities of deoxyspergualin. I. Effect of the long-term administration of the drug on the development of murine lupus.
The effect of 15-deoxyspergualin, a newly developed anti-tumor agent, on the development of spontaneously occurring lupus glomerulonephritis in male BXSB and MRL/lpr mice was examined. The prophylactic effect of 15-deoxyspergualin was evaluated using 8-week-old male BXSB mice. Its therapeutic effect was estimated using male BXSB and MRL/lpr mice of 13 weeks of age. Treatment with 15-deoxyspergualin at a dose of 5 mg/kg for 5 weeks suppressed the increment of IgG-producing cells in the spleen, decreased serum levels of circulating immune complexes assessed by solid-phase C1q-binding assay and effectively prevented the deposition of immune complexes in renal glomeruli estimated by immunofluorescent studies in both strains of mice. 15-Deoxyspergualin was also effective in preventing the massive lymphoproliferation characteristic of MRL/lpr mice as assessed by the weight of mesenteric lymph nodes. It seemed quite valuable that 15-deoxyspergualin drastically suppressed the progress of polyclonal B cell activation in both strains of autoimmune mice, which have different mechanisms leading to B cell activation. These results suggest that 15-deoxyspergualin might be used as a therapeutic agent for human erythematosus.
Makino
M
M
Laboratory of Immunology, Niigata University School of Medicine, Japan.
Fujiwara
M
M
Aoyagi
T
T
Umezawa
H
H
D000818:Animals; D000921:Antibody-Producing Cells / Q000473:pathology; D000936:Antigen-Antibody Complex / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D007166:Immunosuppressive Agents; D007678:Kidney Glomerulus / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000473:pathology / Q000517:prevention & control*; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000473:pathology
D000936:Antigen-Antibody Complex; D006146:Guanidines; D007166:Immunosuppressive Agents; C037258:gusperimus