Effects of a new immunosuppressive agent, FK506, in rats with active Heymann nephritis.
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 groups 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 (less than 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
W
W
Matsukawa
S
S
Hara
F
F
Yoshida
N
N
Suzuki
A
A
Fukatsu
Y
Y
Yuzawa
N
N
Sakamoto
S
S
Matsuo
D000818:Animals; D000906:Antibodies / Q000097:blood; D003401:Creatine / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005921:Glomerulonephritis / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D008871:Microvilli / Q000276:immunology / Q000648:ultrastructure; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D051381:Rats; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
D000906:Antibodies; D007166:Immunosuppressive Agents; D003401:Creatine; D016559:Tacrolimus