Glomerular basement membrane-containing immune complexes stimulate tumor necrosis factor and interleukin-1 production by human monocytes.
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.
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
M C
MC
Vissers
J C
JC
Fantone
R
R
Wiggins
S L
SL
Kunkel
D000936:Antigen-Antibody Complex / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D007678:Kidney Glomerulus / Q000276:immunology* / Q000648:ultrastructure; D009000:Monocytes / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000936:Antigen-Antibody Complex; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha