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Interleukin (IL)-10, but not IL-4 or IL-13, Inhibits Cytokine Production and Growth in Juvenile Myelomonocytic Leukemia Cells¹

Division of Human Immunology, Hanson Centre for Cancer Research, IMVS, P. O. Box 14, Rundle Mall, Adelaide 5000 [P. O. I., A. F. L.], and Department of Microbiology and Infectious Diseases, Flinders University, Bedford Park 5042 [P. H. H., C. S. B.], S. A., Australia

Juvenile myelomonocytic leukemia (JMML) carries a poor prognosis. The endogenous production of cytokines by the JMML cells contributes to their growth and therapeutic resistance. Interleukin (IL)-4, IL-10, and IL-13 inhibit cytokine production in monocytes. We have now studied whether these cytokines can inhibit JMML cell cytokine production, thereby potentially reducing the malignant cell load in this disorder. We found that IL-10, but not IL-4 or IL-13, dose dependently inhibited JMML cell production of the hemopoietic growth factors granulocyte-macrophage colony-stimulating factor, tumor necrosis factor , and IL-1ß. 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 receptors because we could detect mRNAs for the IL-4 and the IL-13 receptor subunits and the IL-2 common subunit in JMML cells. Furthermore, 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 inhibitory 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 production, growth, and viability of JMML cells by IL-10 suggests that this cytokine may have a therapeutic potential in JMML.

¹ Supported in part by the National Health and Medical Research Council and the Anti-Cancer Foundation of the Universities of South Australia. P. O. I. holds a fellowship with The Norwegian Cancer Society.

² To whom requests for reprints should be addressed.

Received 7/29/96. Accepted 12/ 4/96.

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