Interferon-beta reduces proteinuria in experimental glomerulonephritis.

Abstract

Interferon-beta (IFN-beta) is a multifunctional cytokine with immunomodulatory properties. We examined the effect of IFN-beta in three separate rat models of glomerular injury and in cultured human glomerular endothelial cells and podocytes. In nephrotoxic nephritis in WKY rats, recombinant rat IFN-beta started either at induction or after establishment of disease significantly reduced 24-h proteinuria by up to 73% and 51%, respectively, but did not affect serum creatinine. There was a slight reduction in numbers of glomerular macrophages, but no difference in glomerular or tubulointerstitial scarring. In Thy-1 nephritis in Lewis rats, IFN-beta started at induction of disease reduced proteinuria by up to 66% with no effect on numbers of glomerular macrophages, but a reduced number of proliferating cells. In puromycin nephropathy in Wistar rats, IFN-beta started at induction of disease reduced proteinuria by up to 93%, but had no effect on glomerular histology. In cultured cells, human IFN-beta-1a had a dramatic effect on barrier properties, increasing electrical resistance across monolayers of either glomerular endothelial cells or podocytes and decreasing trans-monolayer passage of albumin. In conclusion, these results show that IFN-beta reduces proteinuria in three different rat models of glomerular injury and that its anti-proteinuric action may result from direct effects on cells that comprise the glomerular filtration barrier. These data indicate that IFN-beta may have potential as a therapeutic agent in proteinuric renal disease.

• Authors: Simon C Satchell, Olena Buchatska, Sarah B Khan, Gurjeet Bhangal, Candida H Tasman, Moin A Saleem, Darren P Baker, Roy R Lobb, Jennifer Smith, H Terence Cook, Peter W Mathieson, Charles D Pusey
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 18 Issue 11 Pg. 2875-84 (Nov 2007) ISSN: 1533-3450 [Electronic] United States
• PMID: 17942968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunologic Factors
• Interferon-beta
• Interferon beta-1a

Topics

• Animals
• Cell Culture Techniques
• Disease Models, Animal
• Endothelial Cells (drug effects)
• Glomerular Filtration Rate (drug effects)
• Glomerulonephritis (complications, drug therapy, pathology)
• Humans
• Immunologic Factors (pharmacology, therapeutic use)
• Interferon beta-1a
• Interferon-beta (pharmacology, therapeutic use)
• Kidney Glomerulus (drug effects, metabolism, pathology)
• Proteinuria (etiology, prevention & control)
• Rats
• Rats, Inbred Lew
• Rats, Inbred WKY