Involvement of interleukin-1 in the differentiation-inducing activity of tumor necrosis factor-α on a murine myeloid leukemia (WEHI-3B JCS)

We have shown previously that tumor necrosis factor-α (TNF-α) inhibits the growth and induces the differentiation of a murine myelomonocytic leukemia (WEHI-3B JCS cells) into macrophage-like cells. In this study, using reverse transcription polymerase chain reaction, we found that both endogenous interleukin-1 α and β (IL-1α, IL-1β) mRNA were up-regulated upon TNF-α induction. Exogenous IL-1α and IL-1β also inhibited the growth as well as induced the differentiation of JCS cells, with IL-1β exerting a greater growth-inhibitory effect. Neutralizing anti-IL-1α, anti-IL-1β and anti-TNF-α antibodies were further used to elucidate the role of IL-1α, IL-1β and TNF-α in JCS cell differentiation. The results show that the IL-1α-induced monocytic differentiation of JCS cells was effectively blocked by anti-IL-1α as well as anti-IL-1β antibodies and to a lesser extent by anti-TNF-α antibody. In contrast, the differentiation-inducing effect of IL-1β on JCS cells was only blocked by anti-IL-1β antibody but not by anti-IL-1α or anti-TNF-α antibody. Finally, the TNF-α-induced monocytic differentiation of JCS cells was significantly blocked by anti-TNF-α and to a lesser extent by anti-IL-1α and anti-IL-1β antibodies. Collectively, our results suggest that IL-1β alone may directly trigger JCS cell differentiation whereas the differentiation-inducing effect of IL-1α may be via the endogenous production of IL-1β and/or TNF-α. In addition, IL-1α and IL-1β may be involved, at least in part, in TNF-α-induced monocytic differentiation of the JCS leukemia cells.