Modulation of experimental mesangial proliferative nephritis by interferon-gamma

Kidney Int. 1995 Jan;47(1):62-9. doi: 10.1038/ki.1995.7.


The observation that interferon-gamma (IFN-gamma) inhibits cell proliferation and collagen synthesis of a variety of cell types in culture has suggested that IFN-gamma may be useful in the treatment of fibroproliferative diseases. We administered recombinant IFN-gamma subcutaneously (10(5) U/kg/day for 3 days) to rats, beginning one day after the induction of mesangial proliferative nephritis with anti-Thy 1 antibody. IFN-gamma reduced glomerular (primarily mesangial) cell proliferation by 44% at days 2 and 4 compared to vehicle injected control rats with anti-Thy 1 nephritis (that is, proliferating cells that excluded the macrophage marker, ED-1, P < 0.001). Despite the inhibition of mesangial cell proliferation, IFN-gamma did not reduce the overall extracellular matrix deposition (by silver stain) or deposition of type IV collagen or laminin (by immunostaining) at 4 or 7 days, and glomerular type IV collagen and laminin mRNA levels were increased (1.4 and 1.7-fold) at 4 days relative to controls. The inability of IFN-gamma treatment to reduce mesangial matrix expansion may relate to the fact that IFN-gamma treated rats had a twofold increase in glomerular macrophages (that is, ED-1 positive cells, P < 0.001 at 2 and 4 days) with an increase in oxidant producing cells (day 2, P < 0.05) and a 1.6-fold increase in glomerular TGF-beta mRNA expression (4 days). This suggests that the effect of IFN-gamma to inhibit mesangial cell proliferation in glomerulonephritis may be offset by the ability of IFN-gamma to increase glomerular macrophages and TGF-beta expression. These data also show that IFN-gamma can partly dissociate the mesangial proliferative response from the extracellular matrix expansion in glomerulonephritis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Extracellular Matrix / metabolism
  • Extracellular Matrix Proteins / metabolism
  • Glomerular Mesangium / drug effects
  • Glomerular Mesangium / metabolism*
  • Glomerular Mesangium / pathology
  • Glomerulonephritis, Membranoproliferative / chemically induced
  • Glomerulonephritis, Membranoproliferative / metabolism*
  • Glomerulonephritis, Membranoproliferative / pathology
  • Immunoenzyme Techniques
  • Interferon-gamma / pharmacology*
  • Leukocytes / metabolism
  • Male
  • Platelet-Derived Growth Factor / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Recombinant Proteins
  • Thy-1 Antigens
  • Transforming Growth Factor beta / metabolism


  • Extracellular Matrix Proteins
  • Platelet-Derived Growth Factor
  • RNA, Messenger
  • Recombinant Proteins
  • Thy-1 Antigens
  • Transforming Growth Factor beta
  • Interferon-gamma