Glomerular basement membrane-containing immune complexes stimulate tumor necrosis factor and interleukin-1 production...

The ability of human peripheral blood monocytes to produce tumor necrosis factor (TNF) and interleukin-1 (IL-1) in an in vitro model of immune complex-mediated glomerulonephritis was investigated. When isolated monocytes were incubated with human glomerular basement membrane (GBM) containing anti-GBM immune complexes, both TNF and IL-1 were produced and secreted into the medium. The time course of secretion differed, with IL-1 production being maximal after approximately 8 hours, whereas TNF levels continued to rise for 30 hours. The activities of the monocyte-derived TNF and IL-1 were inhibitable by specific antibodies. No effect was seen when monocytes were incubated separately with either GBM alone or anti-GBM IgG. The levels of TNF and IL-1 released were comparable with those induced by high concentrations of LPS, indicating that production was close to the maximal levels reported for these cells. High levels of TNF and IL-1 also were produced in response to soluble immune complexes. The results show that monocytes can produce significant levels of TNF and IL-1 in response to both surface-bound and soluble immune complexes and provide support for the participation of these monokines in glomerulonephritis.