Growth Inhibition and Augmentation of Mouse Myeloid Leukemic Cell Line Differentiation by Interleukin 1¹

The effect of interleukin 1 (IL 1) on the growth and differentiation of mouse myeloid leukemic cell line (M1) cells into macrophages has been studied. Purified human IL 1β appeared to be growth inhibitory (maximum, 50%) for M1 cells based on cell counts and [³H]thymidine incorporation. The replication of M1 cells was also inhibited by lipopolysaccharide (LPS), and as little as 1 unit/ml IL 1 augmented the growth inhibition by LPS. Although IL 1 inhibited M1 cell growth, it did not induce cell differentiation by the criteria of either effect on expression of Fc receptors or on phagocytic ability. However, IL 1 augmented M1 cell differentiation in conjunction with LPS. At low doses of LPS, addition of IL 1 induced differentiation even though LPS and IL 1 by themselves did not induce differentiation. Cells treated with IL 1 for 1 day and then with LPS for an additional 2 days showed considerable augmentation of Fc receptor expression, while cells treated with the same stimuli in the reverse sequence exhibited only a low level of differentiation. Cells treated with medium alone followed by LPS showed moderate increase in Fc receptor expression. In addition, exposure of cells to IL 1 for at least 16 h was required for IL 1 augmenting effect. Therefore, IL 1 appeared to primarily influence M1 cells to become more sensitive to LPS. Treatment with both of IL 1 and LPS induced differentiation of a LPS-resistant clone of M1 cells, and IL 1 pretreatment rendered the resistant clone to become responsive to the differentiation inducing effect of LPS. Culture supernatants of M1 cells after stimulation with LPS contained IL 1-like activity by thymocyte comitogenic assays. In addition, mouse recombinant IL 1α appeared to have the same activity as purified human IL 1β on the growth and differentiation of M1 cells. These results suggest that IL 1 may play an important role in mouse myeloid leukemic cell differentiation by acting as an autostimulating factor. IL 1 has been shown to be growth inhibitory and cytocidal for several tumor cell lines. Our results therefore suggest that the effects of IL 1 may result in the induction of terminal differentiation of some tumor cells.