Jpn. J. Pharmacol. 70 (1), 43-54 (1996)

Suppression of Experimental Crescentic-Type Anti-Glomerular Basement Membrane (GBM) Nephritis by FK506 (Tacrolimus Hydrate) in Rats

Kazumi Hayashi, Tadashi Nagamatsu, Mikio Ito and Yoshio Suzuki

Department of Pharmacology, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Nagoya 468, Japan

Abstract: The effect of FK506 (tacrolims hydrate), an immunosuppressive agent produced by Streptomyces tsukubaensis, on crescentic-type anti-glomerular basement membrane (GBM) nephritis in rats was investigated. When rats were treated with FK506 from 1 or 20 days after the anti-GBM serum injection, FK506 inhibited the increase in urinary protein excretion. Histological observation demonstrated that FK506 suppressed glomerular alterations. In the FK506-treated rats, antibody production and rat-IgG and C3 deposits on the GBM were significantly less than those in the nephritic control group. FK506 treatment suppressed the accumulation of ED-1-positive cells, CD4-positive cells, CD8-positive cells, interleukin-2 (IL-2)-receptor-positive cells, leukocyte-function-associated antigen-1 (LFA-1)-positive cells and intercellular adhesion molecule-1 (ICAM-1)-expression in nephritic glomeruli. However, in the in vitro study, FK506 failed to inhibit the up-regulated ICAM-1 expression on endothelial cells in response to tumor necrosis factor (TNF)-alpha. On the other hand, IL-2 production from the spleen cells isolated from nephritic rats treated with FK506 was lower than that in the nephritic control rats. These results suggest that FK506 is effective against crescentic-type anti-GBM nephritis and that the antinephritic mechanisms of FK506 is due to the inhibition of intraglomerular accumulation and activation of leukocytes through the suppression of ICAM-1 expression and IL-2 production.

Keywords: Anti-GBM nephritis (crescentic type), FK506, Leukocyte, Interleukin-2, Intercellular adhesion molecule-1

Copyright© The Japanese Pharmacological Society 1996

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