Interleukin- 10 Inhibits the In vitro proliferation of human activated leukemic CDS B-Cells
B-cell chronic lymphocytic leukemia (B-CLL) is characterised by the proliferation and accumulation of sIgM+/CDS' B-cells that fail to progress to the final stages of B-cell development. Despite their developmental arrest, leukemic CD5' B-cells can undergo proliferation in vitro in the presence of different activators including phorbol esters, antibodies to cell surface antigens and human cytokines. Interleukin-I0 (IL-10) has recently been found to inhibit CLL Bcell function in vitro by inducing apoptosis and down-regulating expression of bcl-2. Here, we examined the effect of IL- 10 on proliferation, RNA synthesis, immunoglobulin (IgM) secretion and viability of leukemic CDS B-cells induced by activation with the phorbol ester PMA, alone or in combination with anti-Ig. IL-I0 reduced PMA and PMA/anti-Ig induced proliferation and RNA synthesis by 50430% and 1540% respectively. Although proliferation and RNA synthesis induced by PMA/anti-Ig could be enhanced by the addition of IL-2, IL-4, IL-13, IFN-y or TNF-a, the presence of these cytokines failed to abrogate the IL-lomediated inhibition of leukemic CD5+ B-cell activation. In contrast to the effects on proliferation and RNA synthesis, IL-10 did not inhibit IgM secretion, and had only a minimal effect on the viability of activated cells. Our results indicate that IL-10 inhibits proliferation of leukemic CD5' B-cells by a mechanism distinct from induction of apoptosis and support the proposal for the utilisation of IL-10 in the therapy of B-CLL.
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