The role of iron in the cytotoxicity of tumor necrosis factor.

The effect of iron on the cytotoxicity of tumour necrosis factor-alpha (TNF, cachectin) was examined in L929 cells, which are killed by TNF at low concentrations. In L929 cells, the addition of iron (FeNTA) either prior to or concurrent with the addition of TNF markedly augmented the cytotoxicity of TNF over a wide range of TNF concentrations. Iron alone was not cytotoxic to the cells and did not inhibit protein synthesis. The iron chelator deferoxamine was able to protect against TNF cytotoxicity in L929 cells. Iron chelators also protected L929 cells from the cytotoxicity of TNF plus cycloheximide, suggesting that iron plays a role in this mode of TNF killing as well. TNF did not induce the synthesis of ferritin heavy chain in L929 cells. These experiments demonstrate that cellular iron status affects the ability of TNF to kill sensitive target cells.