IMMUNOSUPPRESSIVE THERAPY OF ORGAN-SPECIFIC NEPHRITIC AUTOIMMUNE-DISEASES WITH 15-DEOXYSPERGUALIN

According to its immunopharmacological profile, 15-deoxyspergualin (15 -DOS) has been investigated as to its disease-modifying activity on Hg Cl2-induced glomerulonephritis (GN) and on tubulointerstitial nephriti s (TIN) in Brown-Norway rats. Both models are induced autoimmune disor ders in which afflicted animals display high levels of serum autoantib odies directed against the glomerular or tubular basement membrane (GB M or TBM), respectively. The diseases are manifested by high serum cre atinine and urea levels with severe proteinuria. In the model of HgCl2 -GN, administration of 15-DOS clearly led to a reduction of proteinuri a and decreased the amount of rat IgG attached to the GBM. Furthermore , a therapeutic effect could be demonstrated when 15-DOS was given aft er the appearance of clinical symptoms. Not only urine-protein values but also anti-laminin antibodies returned to normal levels. Also in th e experimental TIN-model, 15-DOS, either given during the induction ph ase, or even late in the onset of the disease, strongly prevented the proteinuria of this autoimmune disease and inhibited the formation of autoantibodies to TBN.