Intravenous administration of recombinant human IL-10 suppresses the development of anti-thy 1-induced glomerulosclerosis in rats.

AIM: 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. CONCLUSION: 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. LAY ABSTRACT: 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 TGFß-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.

Staphylococcal acid phosphatase binds to endothelial cells via charge interaction; a pathogenic role in Wegener's granulomatosis?

The majority of patients with Wegener's granulomatosis (WG) are chronic nasal carriers of Staphylococcus aureus. Chronic nasal carriage of S. aureus is associated with an increased risk of developing a relapse of the disease. The mechanism by which this occurs is still unknown. We hypothesized that a cationic protein of S. aureus, staphylococcal acid phosphatase (SAcP), acts as a planted antigen and initiates glomerulonephritis and vasculitis in patients with WG. In order to test the hypothesis that SAcP can act as a planted antigen in WG, we studied the ability of SAcP to bind to human umbilical vein endothelial cells (HUVEC) and human glomerular endothelial cells. We also studied whether this binding can be prevented by preincubation with an anionic protein, and whether binding of SAcP activates endothelial cells. We also evaluated whether antibodies in sera of patients with WG are able to bind to endothelial cell-bound SAcP. The results show that SAcP can act as a planted antigen by binding to both types of endothelial cells in a concentration-dependent manner. Binding of concentrations as low as 4 microg/ml can be detected on HUVEC within 5 min of incubation. Binding of SAcP to endothelial cells was charge-dependent but did not activate endothelial cells. Finally, endothelial cell-bound SAcP was recognized by sera of patients with WG. The data suggest a possible pathogenic role for SAcP by acting as a planted antigen thereby initiating glomerulonephritis and vasculitis in patients with WG.