Immunopharmacological studies on experimental glomerulonephritis.

Abstract

Immunopharmacological studies on modified nephrotoxic serum (NTS) nephritis in rats were conducted. The modified NTS nephritis was produced by an intravenous (i.v.) injection of NTS in a subnephrotoxic dose (sub-dose) into the rats which had been previously immunized with rabbit IgG (RGG) and complete Freund's adjuvant (CFA). In previously immunized rats, typical nephritic syndrome was demonstrated with respect to the elevation of urinary protein, serum cholesterol, blood urea nitrogen (BUN) and histopathologic scores of the kidneys. No changes in complement levels were found. By adoptive transfer experiments, it was found that sensitized lymphocytes were essential for causing the nephritis. The potency of the sensitized lymphocytes was reinforced by passing them through a nylon wool or Sephadex G-10 column after treatment with rabbit anti-rat F(ab')2 antibody and complement. The administration of cyclophosphamide, prednisolone, tilorone or cis-1-methyl-4-isohexylcyclohexane carboxylic acid (IG-10) showed a clear remission of nephritis. Cobra venom factor (CoVF) and Cu-chlorophyllin complement inhibitors showed a contradictory efficacy on the nephritis. CoVF which decreased the serum CH50 value did not produce any remission of the nephritis, whereas Cu-chlorophyllin, which slightly decreased CH50 values produced a significant decrease in urinary protein and serum cholesterol. The macrophage-toxic agents carrageenan and dextran sulfate, also did not produce a remission of nephritis. These findings suggest that the participation of T cells is important for the onset of this nephritis and that macrophages and complement do not appear to be involved.