Production of interleukin 1 in glomerular cell cultures from rats with nephrotoxic serum nephritis

To investigate the role of cytokines in the pathogenesis of experimental glomerulonephritis (GN), we examined interleukin 1 (IL-1) activity in isolated glomeruli of rats with an accelerated autologous form of nephrotoxic serum nephritis (NTSN). Glomeruli were isolated and explanted in tissue culture. The prominent feature of the glomerular outgrowth of the glomeruli in the NTSN was the presence of large numbers of type III cells (macrophages). In addition, there were significantly greater numbers of type II (mesangial) cells in culture from the NTSN rats as compared with glomeruli from normal rats, though the numbers of type I (epithelial) cells were the same. IL-1 bioactivity was significantly higher in culture supernatants generated by glomeruli isolated from NTSN animals versus normal animals early in the course of the disease. When glomerular culture supernatants and purified IL-1 were pre-incubated with an anti-IL-1 beta antibody, a parallel decrease of the biological activity was found, suggesting that the biologically active binding sites of the culture supernatants and monocyte-produced IL-1 share some common structure. The administration of a rabbit anti-rat macrophage serum (AMS) prevented the outgrowths of type III cells (macrophages) and type II (mesangial) cells and reduced the production of IL-1 activity in the NTSN rats. In this experimental model IL-1 synthesis, probably by multiple cell types, is present early in the disease process and perhaps may be an important mediator of glomerular immune injury.