Interleukin-1 production by lipopolysaccharide-stimulated glomeruli from rats with nephrotoxic serum nephritis

The objective of the present work was to characterize some aspects of interleukin-1 (IL-1) production by nephritic glomeruli after stimulation with bacterial lipopolysaccharide (LPS). Freshly isolated glomeruli from rats with an accelerated autologous form of nephrotoxic serum nephritis (NTSN) were incubated for 24 h in the presence of LPS. The modified NTSN was produced by an intravenous injection of nephrotoxic serum (NTS) into the rats which had been previously immunized with rabbit IgG and Freund's complete adjuvant. The glomerular cultures of the NTSN rats were found to release significantly increased amounts of IL-1 after LPS stimulation when compared to the values obtained with normal controls and the other control group, consisting of preimmunized rats (rabbit IgG), then given normal rabbit globulin instead of NTS. To block the effect of prostaglandins on the IL-1 assay, we cultured the glomeruli with the addition of 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 anti-rat macrophage serum reduced the production of IL-1 activity in the NTSN rats. Our findings support the notion that at least in NTSN rats activated macrophages are present and probably account for their increased IL-1 activity. This description of IL-1 activity produced by LPS-stimulated nephritic glomeruli may introduce a new element to the early events leading to glomerular inflammation.