The incubation of human blood monocytes with tumor necrosis factor-alpha leads to lysis of tumor necrosis factor-sensitive but not resistant tumor cells.

Abstract

The purpose of this study was to determine whether the incubation of human blood monocytes with tumor necrosis factor (TNF) induces tumoricidal activity. Peripheral blood monocytes isolated by centrifugal elutriation from buffy coats of healthy donors were incubated with lipopolysaccharide (LPS), lipopeptide derived from Escherichia coli (CGP-31362), recombinant human interferon-gamma (rIFN-gamma) plus muramyl dipeptide (MDP) or recombinant human TNF for 24 hr. The human melanoma A375-M (highly sensitive to TNF), A375-P (moderately sensitive to TNF), and A375-R (resistant to TNF) cells were all lysed in vitro by monocytes activated with LPS, CGP-31362, or MDP plus rIFN-gamma. On the other hand, A375-M, but not A375-P or A375-R cells, were lysed by human monocytes incubated with rTNF. After incubation with rTNF, paraformaldehyde-fixed monocytes lysed A375-M cells. Monocytes incubated with LPS, CGP-31362, and MDP plus rIFN-gamma secreted a high level of IL-1 activity into the culture medium, but monocytes incubated with rTNF did not. The cytolytic activities of monocytes incubated with LPS, CGP-31362, and MDP plus rIFN-gamma were not affected by the presence of anti-TNF antiserum, whereas the lysis of A375-M cells by monocytes incubated with rTNF was completely abolished by the presence of anti-TNF antiserum. We conclude that exogenous TNF does not render blood monocytes tumoricidal, but rather that TNF bound to cell-surface receptors can produce lysis of TNF-sensitive cells by a "carryover" mechanism.