Interferon-beta reduces proteinuria in experimental glomerulonephritis.
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.
Satchell
Simon C
SC
Academic Renal Unit, University of Bristol, Southmead Hospital, Bristol, UK. s.c.satchell@bristol.ac.uk
Buchatska
Olena
O
Khan
Sarah B
SB
Bhangal
Gurjeet
G
Tasman
Candida H
CH
Saleem
Moin A
MA
Baker
Darren P
DP
Lobb
Roy R
RR
Smith
Jennifer
J
Cook
H Terence
HT
Mathieson
Peter W
PW
Pusey
Charles D
CD
D000818:Animals; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005921:Glomerulonephritis / Q000150:complications* / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011507:Proteinuria / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D011917:Rats, Inbred Lew; D011921:Rats, Inbred WKY
D007155:Immunologic Factors; D016899:Interferon-beta; D000068556:Interferon beta-1a