Direct and synergistic effects of interleukin 11 on murine hemopoiesis in culture.

Abstract

We have examined the effects of a stromal cell-derived cytokine designated interleukin 11 (IL-11) on the proliferation of murine hemopoietic progenitors in methylcellulose culture. COS cell-conditioned medium containing IL-11 supported formation of granulocyte/macrophage colonies and a small number of multilineage colonies including blast cell colonies in cultures of marrow cells from normal mice. When tested with marrow cells harvested 2 days after injection of 5-fluorouracil at 150 mg/kg, IL-11 enhanced interleukin 3-dependent colony formation, whereas IL-11 alone supported only scant colony formation. Serial observations (mapping studies) of cultures of post-5-fluorouracil spleen cells indicated that the mechanism of the synergistic effect of IL-11 is to shorten the dormant period of stem cells, an effect very similar to that of interleukin 6. When pooled blast cells were plated into medium containing IL-11 and erythropoietin, only macrophage colonies were observed. Thus, IL-11 can directly support the proliferation of committed macrophage progenitors and, like interleukin 6 and granulocyte colony-stimulating factor, act synergistically with interleukin 3 to shorten the Go period of early progenitors.

Expression of a constitutively active erythropoietin receptor in primary hematopoietic progenitors abrogates erythropoietin dependence and enhances erythroid colony-forming unit, erythroid burst-forming unit, and granulocyte/macrophage progenitor growth.

“…2B) but not in the presence of IL-3 (Fig. 2E) (24)(25)(26)(27)(28)(29). After these progenitors become committed to a particular lineage, they require specific growth factors to complete the maturation process; for example, BFU-E and CFU-E require Epo to complete erythroid differentiation (30,31).…”

The expansion of murine bone marrow cells preincubated in hypoxia as an in vitro indicator of their marrow-repopulating ability

“…The combination of IL3 and GM-CSF used in our study supports proliferation of multipotent progenitors 12 and survival in culture, as well as 'proliferation competence', 13 but not cell cycling [14][15][16] of quiescent stem cells. The latter is, indeed, triggered by 'proliferation progression' factors, which include stem cell factor, interleukin-6, interleukin-11, granulocyte colony-stimulating factor, leukemia inhibitory factor and FLT3-ligand.…”

Interleukin-11, an interleukin-6-like cytokine, is a promising predictor for bladder cancer prognosis

“…To date, IL-11 has been characterized most extensively as a cytokine with thrombopoietic activity. It was also shown to have a number of additional biological activities, including stimulation of erythropoeisis (19), activation of megakaryocytes (20), modulation of neuronal phenotypes (21), regulation of macrophage precursors (22), promotion of stem cell development (23) and improved colonization of transplanted murine bone marrow cells (24). In addition, IL-11 is capable of stimulating B cell IgG production (25), and osteoblast-derived IL-11 activates bone-resorbing osteoclasts with an associated decrease in de novo bone formation (26).…”