INTRINSIC RENAL-CELLS ARE THE MAJOR SOURCE OF INTERLEUKIN-1-BETA SYNTHESIS IN NORMAL AND DISEASED RAT-KIDNEY

Background. A number of studies have demonstrated a pathological role for interleukin-1 (IL-1) in experimental models of glomerulonephritis, but the cellular pattern of renal IL-1 production remains poorly char acterized. The aim of this study, therefore, was to identify the cell types expressing IL-1 in normal and diseased rat kidney. Methods. Rena l IL-1 beta expression was examined in normal rats and during a 21-day time course of rat accelerated anti-GEM glomerulonephritis by norther n blotting, in situ hybridization and double Immunohistochemistry. Res ults. Interleukin-1 beta mRNA expression was readily detectable in nor mal rat kidney by northern blot analysis and in situ hybridization. Im munohistochemistry staining demonstrated constitutive IL-1 beta expres sion by glomerular endothelial cells and cortical tubular epithelial c ells. There was a marked increase in whole kidney IL-1 beta mRNA in ra t anti-GBM glomerulonephritis. Glomerular IL-1 beta immunostaining was upregulated, being expressed by podocytes, mesangial cells and infilt rating macrophages, and was particularly prominent within glomerular c rescents. Double staining with the ED1 antibody showed IL-1 beta expre ssion in up to 13% of glomerular macrophages, whereas 48% of macrophag es within crescents stained for IL-1 beta. However, the most marked in crease in IL-1 beta expression was seen in cortical tubular epithelial cells, particularly in areas of tubular damage. In situ hybridization confirmed that tubular IL-1 beta staining was due to local cytokine s ynthesis rather than protein absorption. Conclusions. This study has i dentified constitutive IL-1 beta expression by glomerular endothelium and tubular epithelial cells in normal rat kidney. In addition, the ma rked upregulation of IL-1 beta expression by intrinsic glomerular cell s and tubules in rat anti-GEM disease suggests an important role for t hese cells in IL-1 dependent crescent formation and tubulointerstitial injury.