FK506 is a recently-developed immunosuppressive drug. The aim of the present work was to investigate the effects of FK506 in experimental autoimmune glomerulonephritis (active Heymann nephritis) in rats. Active Heymann nephritis was induced in female Lewis rats by two immunizations with the homologous brush border vesicles (BBVs) at day 0 and day 28 (groups I, II, V, and VI). Rats of group III and IV received the third immunization at day 56. In rats of groups I and III, FK506 was injected (1 mg/kg/day IM) from day 0 for 14 days. In rats of groups II and IV, significant proteinuria was observed (group II, 112.8 mg/16 hours; group IV, 55.4 mg/16 hours) at the time the rats were killed (day 84). Coarse subepithelial immune deposits (IDs) were found in these rats. In contrast, urinary protein excretion remained within normal range (<3.0 mg/16 hours) in groups I and III rats, and tiny subepithelial IDs were only occasionally seen. Circulating anti-BBV antibody levels were markedly lower in group I and III rats than in those of groups II and IV during the period between day 14 and day 56. To investigate the effects of FK506 on the proteinuric rats, FK506 (1 mg/kg/day, IM) was administered every day for 2 weeks beginning on day 56 (group V). When rats given FK506 were compared with the nephritic rats injected with vehicle (saline solution) only (group VI), it was apparent that FK506 prevented the increase of proteinuria (group V, 30.1 ± 6.1 mg/16 hours at day 56, 38.6 ± 9.4 mg/16 hours at day 70; group VI, 29.9 ± 5.6 mg/16 hours at day 56, 65.2 ± 10.2 mg/16 hours at day 70). These data suggested (1) that FK506, when administered at the time of initial immunization, markedly inhibited the induction of Heymann nephritis through the suppression of production of autoantibodies to BBV, and (2) that the suppressive effect lasted even after the second or third immunization with BBV. In addition, FK506 may prevent the worsening of proteinuria in the present model.
|ジャーナル||Journal of Laboratory and Clinical Medicine|
|出版ステータス||Published - 1992|
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