Antinephritic effect of prostaglandin E1 on serum sickness nephritis in rats. (3). Suppression of leukocytes by prostaglandin E1 as a mechanism for preventing immune complex glomerulonephritis.
Serum sickness nephritis was produced in rats by repeated i.v. injections of rabbit serum albumin. After 12 weeks of antigen injection, the rats with proteinuria were subjected to a renal biopsy. Then half of the group was continuously given 300 micrograms/rat/day of PGE1 . alpha-cyclodextrin (PGE1 . CD) with mini osmotic pumps for 3 weeks. PGE1 . CD inhibited the development of glomerulonephritis and the deposition of immune complexes in the glomeruli, although the control group showed developed glomerular alteration and increased immune deposits in the glomeruli in the autopsy specimens. PGE1 . CD particularly improved the intraluminal hypercellularity of the histological findings. In the early stage of this model, 0.5 and 1.0 mg/kg of PGE1 and 6.0, 12.5 and 25.0 mg/kg of azathioprine were administered s.c. and p.o., respectively, for 3 weeks. There was a significant suppression of about 20% in the 1.0 mg/kg PGE1 group on the antibody synthesis as compared with the control group throughout the experimental period, although the inhibition was less than that of azathioprine. In the same experimental protocol, PGE1 significantly suppressed the increase in leukocyte counts; at the third week after PGE1, the number of leukocytes was 25.6 +/- 4.2 X 10(3) in the control group and and 14.1 +/- 3.0 X 10(3) in the 1.0 mg/kg PGE1 group. It is considered that PGE1 could excert the antinephritic effect in this mode through decreasing the leukocyte counts in the circulation and the glomeruli independently of immune deposits in the glomeruli.
D000527:Alprostadil / Q000627:therapeutic use*; D000818:Animals; D000936:Antigen-Antibody Complex / Q000032:analysis; D001379:Azathioprine / Q000494:pharmacology; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D011919:Rats, Inbred Strains; D012713:Serum Sickness / Q000150:complications*
D000936:Antigen-Antibody Complex; D000527:Alprostadil; D001379:Azathioprine