INTERLEUKIN-10 INHIBITS GROWTH AND GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR PRODUCTION IN CHRONIC MYELOMONOCYTIC LEUKEMIA-CELLS/

Autonomous release of hematopoietic growth factors may play a crucial role in the pathogenesis of certain hematological malignancies. Becaus e of its cytokine synthesis-inhibiting action, interleukin 10 (IL-10) could be a potentially useful molecule to affect leukemic cell growth in such disorders. Chronic myelomonocytic leukemia (CMML) cells sponta neously form myeloid colonies (colony-forming units-granulocyte/macrop hage) in methylcellulose, suggesting an autocrine growth factor-mediat ed mechanism. We studied the effect of recombinant human IL-10 (rhIL-1 0) on the in vitro growth of mononuclear cells obtained from periphera l blood or bone marrow of patients with CMML. IL-10 specifically bindi ng to leukemic cells had a profound and dose-dependent inhibitory effe ct on autonomous in vitro growth of CMML cells. IL-10 significantly in hibited the spontaneous growth of myeloid colonies in methylcellulose in 10/11 patients. and autonomous CMML cell growth in suspension in 5/ 5 patients tested. Spontaneous colony growth from CMML cells was also markedly reduced by addition of anti-granulocyte/macrophage colony-sti mulating factor (GM-CSF) antibodies, but not by addition of antibodies against G-CSF, IL-3, or IL-6. IL-10-induced suppression of CMML cell growth was reversed by the addition of exogenous GM-CSF and correlated with a substantial decrease in GM-CSF production by leukemic cells. b oth at the mRNA and protein levels. Our data indicate that IL-10 profo undly inhibits the autonomous growth of CMML cells in vitro most likel y through suppression of endogenous GM-CSF release. This observation s uggests therapeutic evaluation of rhIL-10 in patients with CMML.