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 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 alpha, and IL-1beta. 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 alpha subunits and the IL-2 common gamma 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.
Iversen
P O
PO
Division of Human Immunology, Hanson Centre for Cancer Research, IMVS, Adelaide, Australia.
Hart
P H
PH
Bonder
C S
CS
Lopez
A F
AF
D015703:Antigens, CD / Q000032:analysis; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D018793:Interleukin-13 / Q000494:pharmacology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000494:pharmacology*; D015477:Leukemia, Myelomonocytic, Chronic / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D018123:Receptors, Interleukin / Q000032:analysis; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4
D015703:Antigens, CD; D016207:Cytokines; C508181:IL13RA1 protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D016753:Interleukin-10; D015847:Interleukin-4