Tumor Necrosis Factor Changes Sensitivity of Differentiation of Mouse Leukemia M1 Cells by Lipopolysaccharide

A clone of mouse leukemia M1 cells was induced to differentiate by lipopolysaccharide (LPS) (LPS‐sensitive clone) while another clone of the same cells was resistant (LPS‐resistant clone). LPS and lipid A preparations from Pseudomonas diminuta and Pseudomonas vesicularis were as active as Escherichia coli LPS in the induction of differentiation of the LPS‐sensitive clone. Synthetic lipid A precursor Ia (compound 406), which has no interleukin 1 (IL‐1)‐inducing activity toward monocytes, had strong differentiation‐inducing activity toward the LPS‐sensitive clone. The combined treatment of the LPS‐sensitive clone with LPS and recombinant tumor necrosis factor (rTNF) did not further increase the degree of differentiation induced by LPS alone. By contrast, the LPS‐resistant clone was markedly induced to differentiate by LPS in the presence of rTNF. Combined treatment of the LPS‐resistant clone with LPS and other cytokines such as recombinant IL‐1α, recombinant granulocyte colony‐stimulating factor, and interferon‐γ was not effective in inducing marked synergistic differentiation. These results raise the possibility that rTNF changes the sensitivity of M1 cells to induction of differentiation by LPS.