Production of interleukin-1 by glomerular macrophages in nephrotoxic serum nephritis

This manuscript discusses the important question whether rat glomerular macrophages play a significant, early pathologic role in experimental glomerulonephritis. We use a previously described model of accelerated nephrotoxic serum nephritis (NTSN) induced by an intravenous injection of nephrotoxic serum. Glomerular macrophages were isolated from rat kidneys with NTSN and explanted in tissue cultures. Interleukin-1 (IL-1) bioactivity was significantly higher in culture supernatant generated by glomerular macrophages isolated from NTSN animals than in control animals. To block the effect of prostaglandins on the IL-1 assay, we cultured the macrophages with indomethacin and assayed IL-1 activity in the culture supernatants. The use of indomethacin resulted in a further increase in IL-1 production. The administration of a rabbit antirat macrophage serum prevented the production of IL-1 and reduced the proteinuria in the NTSN rats. Our results indicate that IL-1 protein is increased in the kidneys of NTSN rats and generated by glomerular macrophages. From these observations, we suggest an active role of glomerular macrophages in the pathogenesis of nephritis in this model.