title: Intravenous administration of recombinant human IL-10 suppresses the development of anti-thy 1-induced glomerulosclerosis in rats.
abstract: OBJECTIVE
  Interleukin-10 (IL-10) is a cytokine with potent antifibrotic and anti-inflammatory properties. However, IL-10 has a very short plasma half-life in vivo. This prompted the question whether a short intravenous treatment might have prolonged effects on more chronic processes like sclerosis.
  
  
  METHODS
  Glomerulosclerosis was induced by anti-Thymocyte 1 (Anti-Thy 1) antibody. Four days after induction, an intravenous injection of recombinant human IL-10 (rhIL-10) was given for 3 consecutive days. Untreated rats received vehicle only (phosphate-buffered saline). Parameters of inflammation and fibrosis were assessed at protein and mRNA levels. Untreated rats showed renal histopathological changes as compared to normal rats.
  
  
  RESULTS
  Glomerular matrix expansion and inflammatory cell influx was observed and an increase in glomerular-inducible nitric oxide synthetase and α-smooth muscle actin (α-SMA) were found on the protein level, factors that were clearly attenuated by IL-10 treatment. In particular, the decrease of matrix metalloproteinase-13 levels between days 4 and 7 was completely prevented by IL-10. In contrast, IL-10 did not significantly reduce mRNA levels for procollagen α1(1), α-SMA, and transforming growth factor 1.
  
  
  CONCLUSIONS
  A short-term treatment with rhIL-10 after induction of Anti-Thy 1 antibody nephritic rats attenuated intraglomerular inflammation, and at the protein level also influenced the parameters reflecting matrix deposition and degradation. Despite in fact that IL-10 was shown to be effective in the inhibition of matrix deposition, it had no beneficial effect on proteinuria.
  Interleukin-10 is a cytokine with potent antifibrotic and anti-inflammatory properties. Its short plasma half-life raises the question whether a short intravenous treatment might have prolonged effects on chronic disease like sclerosis. To confirm this, recombinant human interleukin-10 was used to treat glomerulosclerosis in rats. The disease was induced by Anti-Thy 1 antibody. Four days after induction, an intravenous injection of IL-10 was given for 3 consecutive days. Untreated rats received vehicle only (phosphate-buffered saline). Parameters of inflammation and fibrosis were assessed at protein and mRNA levels. In this study, untreated rats showed renal histopathological changes as compared to normal rats. Glomerular matrix expansion and inflammatory cell influx was observed, and increases in glomerular nitric oxide synthetase and α-smooth muscle actin α-SMA were found on the protein level. In contrast, treated rats clearly showed reduction of all these parameters. In particular, the decrease of anti-matrix metalloproteinase-13 (MMP-13) levels between days 4 and 7 was completely prevented by IL-10. However, IL-10 did not significantly reduce mRNA levels for procollagen α1(1), α-SMA, and TGFβ-1. Based on these results, it can be concluded that a short-term treatment with rhIL-10 after induction of Anti-Thy 1 antibody in nephritic rats attenuated intraglomerular inflammation, and at the protein level also influenced the parameters reflecting matrix deposition and degradation. Despite in fact that IL-10 was shown to be effective in the inhibition of matrix deposition, it had no beneficial effect on proteinuria.
authors.affiliation: Department of Pharmacokinetics and Drug Delivery, Groningen University Institute for Drug Exploration (GUIDE), University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Rachmawati
authors.forename: L
authors.initials: L
authors.lastname: Beljaars
authors.forename: C
authors.initials: C
authors.lastname: Reker-Smit
authors.forename: H I
authors.initials: HI
authors.lastname: Bakker
authors.forename: A M
authors.initials: AM
authors.lastname: Van Loenen-Weemaes
authors.forename: M N
authors.initials: MN
authors.lastname: Lub-De Hooge
authors.forename: K
authors.initials: K
authors.lastname: Poelstra
mesh_terms: D000818:Animals; D005921:Glomerulonephritis / Q000188:drug therapy; D006801:Humans; D007262:Infusions, Intravenous; D016753:Interleukin-10 / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000494:pharmacology; D011507:Proteinuria; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016753:Interleukin-10; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D020778:Matrix Metalloproteinase 2