INTERLEUKIN (IL)-10, BUT NOT IL-4 OR IL-13, INHIBITS CYTOKINE PRODUCTION AND GROWTH IN JUVENILE MYELOMONOCYTIC LEUKEMIA-CELLS

Juvenile myelomonocytic leukemia (JMML) carries a poor prognosis, The endogenous production of cytokines by the JMML cells contributes to th eir growth and therapeutic resistance, Interleukin (IL)-4, IL-10, and IL-13 inhibit cytokine production in monocytes, We have now studied wh ether these cytokines can inhibit JMML cell cytokine production, there by potentially reducing the malignant cell load in this disorder, We f ound that IL-10, but not IL-4 or IL-13, dose dependently inhibited JMM L cell production of the hemopoietic growth factors granulocyte-macrop hage colony-stimulating factor, tumor necrosis factor alpha, and IL-1 beta. Similarly, IL-10, but not IL-4 or IL-13, suppressed JMML colony formation and cell viability, This was not due to the absence of recep tors because we could detect mRNAs for the IL-4 and the IL-13 receptor cu subunits and the IL-2 common gamma subunit in JMML cells, Furtherm ore, the receptors were active since both IL-4 and IL-13 up-regulated surface expression of MHC class II and down-regulated CD14 antigens on JMML cells and monocytes, Unlike activated monocytes, the JMML cells did not produce IL-10. It is suggested that the loss of cytokine inhib itory effects of IL-4 and IL-13 could play a role in the pathogenesis of this disorder, On the other hand, the inhibition of cytokine produc tion, growth, and viability of JMML cells by IL-10 suggests that this cytokine may have a therapeutic potential in JMML.