INTERLEUKIN-13 - NOVEL ROLE IN DIRECT REGULATION OF PROLIFERATION ANDDIFFERENTIATION OF PRIMITIVE HEMATOPOIETIC PROGENITOR CELLS

The recently cloned interleukin 13 (IL-13) shares most investigated bi ological activities on B lymphocytes and monocytes with IL-4. In this study we investigated for the first time the potential role of IL-13 i n the regulation of the growth of hematopoietic progenitor cells. IL-1 3 enhanced stem cell factor (SCF)-induced proliferation of Lin(-)Sca-1 (+) bone marrow progenitor cells more potently than IL-4. The effect o f IL-13 was purely synergistic, since IL-13 alone stimulated no colony formation. Single cell experiments suggested that the synergistic eff ect of IL-13 on Lin(-)Sca-1(+) progenitors was directly mediated. In c ontrast, IL-13 had no synergistic activity on SCF-induced proliferatio n of the more mature Lin(-)Sca-1(-) progenitor cells. Thus, the clonin g frequency in response to SCF + IL-13 was at least 20-fold higher in the Lin(-)Sca-1(+) than the Lin(-)Sca-1(-) progenitor cell population. Furthermore, IL-13 but not IL-4 synergistically enhanced colony forma tion of Lin(-)Sca(-)1(+) progenitors in response to granulocyte/macrop hage colony-stimulating factor (GM-CSF) (threefold), whereas both IL-4 and IL-13 enhanced G-CSF-induced colony formation (threefold), and ne ither of the two significantly affected CSF-1 and IL-3-induced prolife ration. Finally, whereas stimulation of Lin(-)Sca-1( )progenitors by S CF + G-CSF resulted in the formation of 90% granulocytes, the addition of IL-13 resulted in the production of macrophages exclusively. This novel effect on differentiation was directly mediated, shared with IL- 4, and could not be observed on Lin(-)Sca-1(-) progenitor cells. Colle ctively, these findings indicate a novel role of IL-13 in early myelop oiesis, partially overlapping but also different from that of IL-4.