Difluoromethylornithine therapy of female NZB/W mice.
We studied the effects of difluoromethylornithine (DFMO), an experimental drug that inhibits the biosynthesis of natural polyamines, on anti-DNA antibody production, immunoglobulin synthesis, proteinuria, and blood urea nitrogen (BUN) in lupus-prone female NZB/W mice. Administration of 1% of the drug in drinking water reduced anti-DNA antibody levels by about 80% of that of untreated mice of the same strain. There was a reduction of IgG and IgA levels in older DFMO treated mice, whereas IgM level was not affected. Proteinuria and BUN were also significantly reduced in treated mice. Moreover, DFMO treatment reduced the concentration of putrescine and spermidine in spleen cells. Our results suggest that polyamine biosynthesis inhibition by DFMO may provide a new approach to the treatment of lupus.
Thomas
T J
TJ
Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903.
Messner
R P
RP
D000818:Animals; D000974:Antibodies, Antinuclear / Q000378:metabolism; D001806:Blood Urea Nitrogen; D000518:Eflornithine / Q000627:therapeutic use*; D005260:Female; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008177:Lupus Vulgaris / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011507:Proteinuria / Q000378:metabolism; D011700:Putrescine / Q000378:metabolism; D013095:Spermidine / Q000378:metabolism; D013154:Spleen / Q000737:chemistry / Q000166:cytology / Q000378:metabolism
D000974:Antibodies, Antinuclear; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine