Recombinant tumor necrosis factor stimulates interleukin-1 production in glomerular cultures from rats with nephrotoxic serum nephritis

We have investigated the effect of recombinant tumor necrosis factor (r-TNF) on the release of interleukin-1 (IL-1) in glomerular cultures from rats with an accelerated autologous form of nephrotoxic serum nephritis (NTSN). Freshly isolated glomeruli from the NTSN rats were incubated for 24 h in the presence of r-TNF. When the glomeruli were activated by r-TNF substantial amounts of IL-1 could be detected in the supernatants as measured by the mouse thymocyte assay. The r-TNF-induced IL-1 activity was significantly higher in rats with NTSN than those in normal controls and the other control group, consisting of preimmunized rats (rabbit IgG), then given normal rabbit globulin instead of NTS. To avoid the effect of prostaglandins on the IL-1 assay, we cultured the glomeruli with addition of indomethacin and assayed IL-1 activity in the culture supernatants. This cyclooxygenase inhibitor augmented r-TNF-induced IL-1 production. Our data suggest that r-TNF can serve as a potent stimulator of IL-1 synthesis in glomerular cultures from rats with NTSN.