Interferon-β reduces proteinuria in experimental glomerulonephritis

• Published in: Journal of the American Society of Nephrology 2007-11, Vol.18 (11), p.2875-2884
• Main Authors: SATCHELL, Simon C, BUCHATSKA, Olena, MATHIESON, Peter W, PUSEY, Charles D, KHAN, Sarah B, BHANGAL, Gurjeet, TASMAN, Candida H, SALEEM, Moin A, BAKER, Darren P, LOBB, Roy R, SMITH, Jennifer, TERENCE COOK, H
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Culture Techniques; Disease Models, Animal; Endothelial Cells - drug effects; Glomerular Filtration Rate - drug effects; Glomerulonephritis; Glomerulonephritis - complications; Glomerulonephritis - drug therapy; Glomerulonephritis - pathology; Humans; Immunologic Factors - pharmacology; Immunologic Factors - therapeutic use; Interferon beta-1a; Interferon-beta - pharmacology; Interferon-beta - therapeutic use; Kidney Glomerulus - drug effects; Kidney Glomerulus - metabolism; Kidney Glomerulus - pathology; Medical sciences; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Proteinuria - etiology; Proteinuria - prevention & control; Rats; Rats, Inbred Lew; Rats, Inbred WKY; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.2006101104

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.