Administration of dehydroepiandrosterone sulfate retards onset but not progression of autoimmune disease in NZB/W mice.
NZB/W mice spontaneously develop an autoimmune disease characterized by the formation of anti-DNA antibodies and subsequent development of a fatal immune complex-mediated glomerulonephritis. Treatment of NZB/W F1 female mice with DHEAS, a precursor of DHEA, beginning at 2 months of age delayed the onset of autoimmune disease and prolonged survival. Animals treated with DHEAS beginning at 2 months of age had significantly lower anti-dsDNA serum antibody titers when compared to controls. Interestingly, DHEAS treatment had no effect on titers of anti-phosphatidylcholine (PtC) "natural" antibodies. Serum levels of IL-10, which increase with onset of disease, were also significantly reduced in mice treated with DHEAS beginning at 2 months of age. In contrast, if DHEAS treatment was started at 6 months of age, there was no effect on mortality rates. In addition, treatment of animals with DHEAS beginning at 6 months of age did not lower serum titers of anti-dsDNA and had no ameliorating effect on anti-PtC antibody production. Serum levels of IL-10 were also unaffected in mice treated with DHEAS beginning at 6 months of age. Together, these data suggest that parenteral administration of DHEAS is effective at delaying autoimmune disease and prolonging survival when given prior to the onset of symptoms. However, DHEAS treatment does not affect the course of disease when treatment begins after the onset of disease. We propose that DHEA(S) therapy used under similar conditions would not provide a clinically beneficial effect in the specific symptoms of immune complex-mediated glomerulonephritis.
Norton
S D
SD
Pharmadigm, Inc., Salt Lake City, Utah 84109, USA.
Harrison
L L
LL
Yowell
R
R
Araneo
B A
BA
D000367:Age Factors; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D016175:B-Lymphocyte Subsets / Q000276:immunology; D019314:Dehydroepiandrosterone Sulfate / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007075:Immunoglobulin M / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D051379:Mice; D008814:Mice, Inbred NZB; D010713:Phosphatidylcholines / Q000276:immunology
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D007075:Immunoglobulin M; D010713:Phosphatidylcholines; D016753:Interleukin-10; D019314:Dehydroepiandrosterone Sulfate