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 b y the forma tion 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 signific antly lower anti-dsDNA serum antibody titers when compared to controls . Interestingly, DHEAS treatment had no effect on titers of anti-phosp hatidylcholine (PtC) ''natural'' antibodies. Serum levels of LL-IO, wh ich 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 o n mortality rates. In addition, treatment of animals with DHEAS beginn ing at 6 months of age did not lower serum titers of anti-dsDNA and ha d 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 adminis tration of DHEAS is effective at delaying autoimmune disease and prolo nging survival when given prior to the onset of symptoms. However, DHE AS treatment does not affect the course of disease when treatment begi ns after the onset of disease. We propose that DHEA(S) therapy used un der similar conditions would not provide a clinically beneficial effec t in the specific symptoms of immune complex-mediated glomerulonephrit is.