title: Interferon-gamma inhibits experimental renal fibrosis.
abstract: Interferon-gamma inhibits experimental renal fibrosis.
  
  
  BACKGROUND
  Recent evidence has implicated myofibroblasts as a cell type responsible for the laying down of extracellular matrix components during fibrosis in a number of organs. In this study, we examined the capacity of interferon-gamma (IFN-gamma) to inhibit the activation of fibroblasts to the myofibroblastic phenotype and hence reduce the extent of renal scarring in the rat subtotal nephrectomy (SNx) model using a novel method of intrarenal delivery.
  
  
  METHODS
  Rats were divided into four groups: sham, SNx (group 1), SNx + drug vehicle (group 2) and SNx + IFN-gamma (400 units/day; group 3) for 30 days. Rats were sacrificed on days 15, 30, 45, and 90 following SNx.
  
  
  RESULTS
  Clinical data showed a marked reduction in proteinuria in the group treated with IFN-gamma (161 vs. 280 mg/24 hr by day 45, P < 0.01) and a preservation of the creatinine clearance (1.16 vs. 0. 84 ml/min by day 45, P < 0.05) when compared to the SNx or SNx + vehicle groups throughout the time course. Immunohistochemical staining for alpha-smooth muscle actin (alpha-SMA) revealed a reduction in myofibroblastic cell types (6.5 +/- 3.1% glomerular alpha-SMA in group 3 compared with 14.8 +/- 4.2% glomerular alpha-SMA in group 2, P < 0.05, 3.8 +/- 1.4% tubulointerstitial alpha-SMA in group 3 compared with 8.8 +/- 2.0% tubulointerstitial alpha-SMA in group 2 on day 45, P < 0.05). There was also a reduction in immunostaining for collagens III and IV in the IFN-gamma-treated group. Scoring for both glomerulosclerosis and tubulointerstitial fibrosis in the IFN-gamma group (group 3) was lower than the other two operated groups.
  
  
  CONCLUSIONS
  We conclude that IFN-gamma, administered at a dose of 400 units/day, has a strong inhibitory effect on myofibroblasts and that as a possible result of this action, renal fibrosis is reduced and renal function is preserved in the rat SNx model. The IFN-gamma renoprotective effect lasted only for the extent of its administration and subsided when discontinued.
authors.affiliation: Division of Clinical Sciences NGH, Sheffield Kidney Institute, University of Sheffield, Northern General Hospital, England, United Kingdom. s.d.oldroyd@sheffield.ac.uk
authors.forename: S D
authors.initials: SD
authors.lastname: Oldroyd
authors.forename: G L
authors.initials: GL
authors.lastname: Thomas
authors.forename: G
authors.initials: G
authors.lastname: Gabbiani
authors.forename: A M
authors.initials: AM
authors.lastname: El Nahas
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000494:pharmacology*; D002921:Cicatrix / Q000473:pathology / Q000517:prevention & control; D003094:Collagen / Q000032:analysis; D003404:Creatinine / Q000378:metabolism; D005347:Fibroblasts / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D005355:Fibrosis; D007124:Immunoenzyme Techniques; D015918:Infusion Pumps, Implantable; D007371:Interferon-gamma / Q000032:analysis / Q000494:pharmacology*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000473:pathology* / Q000517:prevention & control; D008264:Macrophages / Q000737:chemistry; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000199:Actins; D000970:Antineoplastic Agents; D007371:Interferon-gamma; D003094:Collagen; D003404:Creatinine