Production of interleukin-1 in macrophage cultures from rats with nephrotoxic serum nephritis

To investigate the role of cell-mediated immunity in the pathogenesis of experimental glomerulonephritis, we examined interleukin-1 (IL-1) activity in the culture supernatant of lipopolysaccharide-stimulated peritoneal macrophages from rats with an accelerated autologous form of nephrotoxic serum nephritis (NTSN). Modified NTSN was produced by an intravenous injection of nephrotoxic serum (NTS) into the rats which had previously been immunized with rabbit IgG and Freund's complete adjuvant. It was found that the NTSN rats had significantly increased levels of IL-1 activity when compared to the values obtained with normal controls and the other control group, consisting of pre-immunized rats (rabbit IgG), then given normal rabbit globulin instead of NTS. The administration of a rabbit anti-rat macrophage serum reduced the production of IL-1 activity in the NTSN rats. In this experimental model IL-1 synthesis by peritoneal macrophages is present early in the disease process and may be an important mediator of glomerular immune injury.