Suppression of experimental crescentic glomerulonephritis by interleukin-10 gene transfer

Background. Investigated were effects of overexpression of interleukin-10 (IL-10) on the outcome and progression of crescentic glomerulonephritis in Wistar-Kyoto (WKY) rats. Methods. Rats were singly or simultaneously injected with antiglomerular basement membrane (a-GBM) antibody and adenoviral vector encoding rat IL-10 (Ad-rIL-10) or LacZ (Ad-LacZ) (3x10(10) pfu/rat) intravenously, and were sacrificed at day 7. Their kidneys and other organs were isolated and examined by histology and immunohistochemistry. The In vivo expression of IL-10 mRNA in the liver of Ad-rIL-10-injected rats was confirmed by both reverse transcription-polymerase chain reaction (RT-PCR) and ribonuclease protection assay analysis and its translated protein was measured in the serum by enzyme-linked immunosorbent assay (ELISA). Results. The exogenous IL-10 mRNA was strongly expressed in the liver in a dose-dependent manner and was intense at days 4 and 7 but was less intense at day 14. Ad-rIL-10 treatment significantly reduced the incidence of glomerular crescent formation from 67%+/-1.9% in a-GBM antibody-treated group or 69.8%+/-1.9% in a-GBM antibody+Ad-LacZ-treated group to 21.6%+/-1.8% (P<0.001), the glomerular infiltration of macrophages from 35.7 +/- 6.3 cell s/gcs (a-GBM antibody) or 37.6 +/- 8.6 cells/gcs (both a-GBM antibody+Ad-LacZ) to 17.9 +/- 5.5 cells/gcs (P<0.001), that of major histocompatibility complex (MHC) class II-positive cells from 14.4+/-5.3 cells/gcs (a-GBM antibody) or 15+/-4.6 cells/gcs (a-GBM antibody+Ad-LacZ) to 5.7+/-2.3 cells/gcs (P<0.0001) at day 7, the glomerular and immune tissue expression of IL-1 mRNA, as well as the proteinuria from 159.0 +/- 22.7 mg/24 hours (a-GBM antibody) or 166 +/- 28 mg/24 hours (a-GBM antibody+Ad-LacZ) to 42.2 +/- 35.2 mg/24 hours (P<0.01) at day 7. The serum creatinine and blood urea nitrogen levels were also reduced from 2.8+/-0.1 mg/dL (a-GBM antibody) or 2.8+/-0.1 mg/dL (a-GBM antibody+Ad-LacZ) to 1.0+/-0.1 mg/dL (P<0.001) and from 63.2 +/- 8.9 mg/dL (a-GBM antibody) or 61.3 +/- 5.2 mg/dL (a-GBM antibody+Ad-LacZ) to 27.0 +/- 4.5 mg/dL (P<0.001), respectively. However, the glomerular accumulation of CD8(+) cells was unaffected: 5.4+/-1.1 cells/gcs (a-GBM antibody+Ad-rIL-10), 5.9+/-1.5 cells/gcs (a-GBM antibody), and 5.8+/-1.1 cells/gcs (a-GBM antibody+Ad-LacZ) (P=NS). Conclusion. IL-10 gene transfer significantly attenuated the glomerular lesions and injury in the anti-GBM crescentic glomerulonephritis of WKY rats.