Disparate effects of interleukin 11 and thrombopoietin on megakaryocytopoiesis in vitro

The effects of interleukin-11 (IL-11) and thrombopoietin (TPO) on murine me gakaryocytopoiesis were studied using a serum-free culture system. Acting a lone, both IL-11 and TPO increased the number of acetylcholinesterase (AchE )(+) cells (megakaryocytes), the latter being more potent than the former. TPO, but not IL-11, increased the mean AchE activity per megakaryocyte (Ach E activity/megakaryocyte). TPO increased both the number of megakaryocytes with high ploidy, and of those with low ploidy. In contrast, IL-11 increase d only the number of megakaryocytes with high ploidy. The effect of TPO on megakaryocyte ploidy was stronger than that of IL-11. Both IL-11 and TPO in creased the proportion of large megakaryocytes, but the latter was more pot ent than the former. While the stimulatory effects of IL-11 and TPO on the number of megakaryocytes were enhanced by IL-3 or stem cell factor (SCF), s ynergism of IL-11 or TPO with IL-3 or SCF in stimulating AchE activity/mega karyocyte was inconsistent. IL-11 and TPO stimulated the formation of colon y-forming units of megakaryocyte in the presence of IL-3, but not alone, wi th similar maximum colony numbers for both cytokines. Our findings thus dem onstrate that IL-11 principally stimulates megakaryocyte maturation rather than the proliferation of megakaryocytes, whereas TPO stimulates both. (C) 2001 Academic Press.