TNF-ALPHA AND IL-6 INDUCE DIFFERENTIATION IN THE HUMAN BASOPHILIC LEUKEMIA-CELL LINE KU812

The basophilic leukaemia cell line KU8l2 can be induced to differentia te into basophil-like cells in vitro when exposed to supernatant from the Mo T-cell line. KU812 cells express affinity receptors for IgE, pr oduce histamine and tryptase and have the capacity for IgE-mediated hi stamine release. In this study we have examined the cytokines, produce d by the Mo cell line, which are responsible for the observed differen tiation-inducing effect in the KU812 cell line. It was shown that inte rleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) induced differentiation in the KU812 cells and that these cytokines were respo nsible for the differentiation-inducing effect of the Mo supernatant. Other cytokines tested, IL-1 beta, IL-2, IL-4, IL-5, IL-8, granulocyte -macrophage colony-stimulating factor (GM-CSF) and nerve growth factor (NGF) were without effect on the KU812 cells. KU812 was also shown to express receptors for both TNF-alpha and IL-6 after 3 days cultivatio n with conditioned media from the Mo T-cell line. Untreated cells show ed no detectable levels of TNF-alpha or 1L-6 receptors indicating indu ction of these receptors during differentiation. Spontaneous different iation was shown to occur under serum-free conditions which may be the result of endogenous IL-6 production through an autocrine loop. The a ctivity of TNF-alpha and IL-6 could be blocked by specific monoclonal antibodies (mAb) to the respective cytokine.