Leukemia inhibitory factor and interleukin-11 promote maturation of murine and human megakaryocytes in vitro

The growth‐promoting activities of optimally stimulating concentrations of leukemia inhibitory factor (LIF) and interleukin‐11 (IL‐11), a stromal cell‐derived cytokine, on megakaryocytes in liquid marrow cultures were compared to interleukin‐6 (IL‐6), a known megakaryocytic maturation factor. Maximally stimulating concentrations of LIF (25 ng/ml), IL‐11 (10 ng/ml), or IL‐6 alone (10 ng/ml) promoted an 81, 157, and 153% increase, respectively, in acetylcholinesterase (AchE) activity in murine serum‐free cultures compared with controls (n = 5). In combination with 25 U/ml murine interleukin‐3 (IL‐3), LIF, IL‐6, and IL‐11 showed increases, respectively, of 35%, 49%, and 174% in AchE activity compared with IL‐3 alone (n = 4). Flow cytometric analysis of 4‐day‐old cultures showed that LIF alone had minimal effect on megakaryocytic ploidy, whereas IL‐11 and IL‐6 alone markedly augmented high ploidy cells. Enumeration of cells stained for AchE showed that IL‐11 increased the numbers of Mks in comparison to LIF, IL‐6 or controls by up to 59%. Moreover, a twofold increment in Mk number was noted when IL‐11 was used in combination with IL‐3 (compared with either IL‐3 alone of IL‐3 + IL‐6). Flow cytometric ploidy analysis of 8‐day‐old human liquid marrow cultures showed that either LIF, IL‐11, or IL‐6 alone markedly augmented the percentage of 32N cells compared with cultures containing only human IL‐3. The data suggest that LIF and IL‐11 promote murine and human Mk maturation in vitro, although the effect of IL‐11 exceeds that of LIF in mice. Despite the comparable influence of IL‐11 and IL‐6 on Mk ploidy, IL‐11 has the additional characteristic of enhancing the number of Mks, particularly in combination with IL‐3. © 1992 Wiley‐Liss, Inc.