FK506 ameliorates proteinuria and glomerular lesions induced by anti-Thy 1.1 monoclonal antibody 1-22-3

Yohei Ikezumi, Katsue Kanno, Hiroko Koike, Masayuki Tomita, Makoto Uchiyama, Fujio Shimizu, Hiroshi Kawachi

研究成果: Article査読

32 被引用数 (Scopus)

抄録

Background. We have previously reported that CD4 T lymphocytes and their cytokines contribute to development of Thy 1.1 glomerulonephritis (GN). FK506 is reported to suppress the production of Th1 cytokines. The aims of this study were to elucidate the role of Th1 cytokines on mesangial alteration and to examine whether FK506 is available for therapy of mesangial proliferative GN. Methods. The effects of daily treatments of FK506 from day -5 and from day +1 of Thy 1.1 GN induction on glomerular alterations were analyzed. Results. FK506 treatment with 1.0 and 0.3 mg/kg body weight (BW) daily from day 1 to day 4 significantly reduced the glomerular expression of mRNA for interferon-γ (IFN-γ 1.0 mg/kg BW FK506, 32.4% to the placebo group, P < 0.01) and IL-2 (55.6%, P < 0.01) on day 5. FK506 treatment from day -5 of GN induction reduced proteinuria and glomerular alteration in a dose-dependent manner. Although no side effects were detected in rats with 0.3 mg/kg BW of FK506 treatment from day +1, the treatment also ameliorated proteinuria (day 14, 3.7 ± 0.89 vs. 19.8 ± 12.3 mg/100 g BW/day P < 0.05) and glomerular alterations [total cell number, 63.1 ± 3.1 vs. 80.2 ± 7.4, P < 0.01; matrix expansion, 0.90 ± 0.30 vs. 1.34 ± 0.27, P < 0.05; α-smooth muscle actin (αSMA) expression; 1.20 ± 0.12 vs. 1.96 ± 0.29, P < 0.01] on day 14. Conclusion. Th1 cytokines may play an important role in the development of mesangial proliferative glomerulonephritis, and could be targets for therapy. FK506 might be available for clinical use.

本文言語English
ページ(範囲)1339-1350
ページ数12
ジャーナルKidney International
61
4
DOI
出版ステータスPublished - 2002
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腎臓病学

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