title: FK506 ameliorates proteinuria and glomerular lesions induced by anti-Thy 1.1 monoclonal antibody 1-22-3.
abstract: 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-gamma (IFN-gamma; 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; alpha-smooth muscle actin (alphaSMA) expression; 1.20 +/- 0.12 vs. 1.96 +/- 0.29, P < 0.01] on day 14.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cell Biology, Institute of Nephrology, and Department of Pediatrics, Faculty of Medicine, Niigata University, Niigata, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ikezumi
authors.forename: Katsue
authors.initials: K
authors.lastname: Kanno
authors.forename: Hiroko
authors.initials: H
authors.lastname: Koike
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tomita
authors.forename: Makoto
authors.initials: M
authors.lastname: Uchiyama
authors.forename: Fujio
authors.initials: F
authors.lastname: Shimizu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011507:Proteinuria / Q000188:drug therapy* / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D018417:Th1 Cells / Q000378:metabolism; D018800:Thy-1 Antigens / Q000276:immunology*; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D007166:Immunosuppressive Agents; D018800:Thy-1 Antigens; D016559:Tacrolimus