The growth-promoting activities of optimally stimulating concentrations of leukemia inhibitory factor (LIF) and interleukin-I 1 (IL-1 I ) , 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 ngiml), IL-I 1 (1 0 ngiml), or IL-6 alone (1 0 ng/ml) promoted an 81, 157, and 153% increase, respectively, in acetylcholine5terase (AchE) activity in murine serum-free cultures cornpared with controls (11 = 5). In combination with 2.5 Uiml murine interleukin-3 (IL-3), LIF, 11.-6, and IL-I 1 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-I 1 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-I 1, 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-I 1 promote murine and human M k maturation in vitro, although the effect of IL-l 1 exceeds that of LIF in mice. Despite the comparable influence of IL-11 and IL-6 on M k ploidy, IL-11 ha5 the additional characteristic of enhancing the number of Mks, particularly in combination with IL-3. CC? 1992 WiIcy-Liss. Inc.