INVOLVEMENT OF INTERLEUKIN-1 IN THE DIFFERENTIATION-INDUCING ACTIVITYOF TUMOR-NECROSIS-FACTOR-ALPHA ON A MURINE MYELOID-LEUKEMIA (WEHI-3B JCS)

We have shown previously that tumor necrosis factor-alpha (TNF-alpha) inhibits the growth and induces the differentiation of a murine myelom onocytic leukemia (WEHI-3B JCS cells) into macrophage-like cells. In t his study, using reverse transcription polymerase chain reaction, we f ound that both endogenous interleukin-1 alpha and beta (IL-1 alpha, IL -1 beta) mRNA were up-regulated upon TNF-alpha induction. Exogenous IL -1 alpha and IL-1 beta also inhibited the growth as well as induced th e differentiation of JCS cells, with IL-1 beta exerting a greater grow th-inhibitory effect. Neutralizing anti-IL-1 alpha, anti-IL-1 beta and anti-TNF-alpha antibodies were further used to elucidate the role of IL-1 alpha, IL-1 beta and TNF-alpha in JCS cell differentiation. The r esults show that the IL-1 alpha-induced monocytic differentiation of J CS cells was effectively blocked by anti-IL-1 beta as well as anti-IL- 1 beta antibodies and to a lesser extent by anti-TNF-alpha antibody. I n contrast, the differentiation-inducing effect of IL-1 beta on JCS ce lls was only blocked by anti-IL-1 beta antibody but not by anti-IL-1 a lpha or anti-TNF-alpha antibody. Finally, the TNF-alpha-induced monocy tic differentiation of JCS cells was significantly blocked by anti-TNF -alpha and to a lesser extent by anti-IL-1 alpha and anti-IL-1 beta an tibodies. Collectively, our results suggest that IL-1 beta alone may d irectly trigger JCS cell differentiation whereas the differentiation-i nducing effect of IL-1 alpha may be via the endogenous production of I L-1 beta and/or TNF-alpha. In addition, IL-1 alpha and IL-1 beta may b e involved, at least in part, in TNF-alpha-induced monocytic different iation of the JCS leukemia cells.