Hematopoietic Cytokines

Hematopoietic cytokines are large family of extracellular ligands that stimulate hematopoietic cells to differentiate into eight principle types of blood cells. Numerous cytokines are involved in the regulation of hematopoiesis within a complex network of positive and negative regulators. Some cytokines have very narrow lineage specificities of their actions, while many others have rather broad and overlapping specificity ranges.¹

Listed within this section are the cytokines whose predominant action appears to be the stimulation or regulation of hematopoietic cells. This includes GM-CSF, G-CSF, M-CSF, interleukins, EPO and TPO. There are a number of other cytokines that exert profound effects on the formation and maturation of hematopoietic cells, which include stem cell factor (SCF), flt-3/flk-2 ligand (FL) and leukemia inhibitory factor (LIF). Other cytokines or ligands such as jagged-1, transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) also play significant roles in modulating hematopoiesis.

Table 1 Regulation of Hematopoiesis by Cytokines

Cytokine	Function in hematopoiesis
Erythropoietin (EPO)	Red blood cell production
Flt-3	Stimulation of stem and developing dendritic cells
Granulocyte-macrophage colony stimulating factor (GM-CSF)	Stimulation of diverse set of granulocyte-macrophage colonies
Granulocyte-colony stimulating factor (G-CSF)	granulocytic colony stimulation
Interleukin-2 (IL-2)	T-cell proliferation
Interleukin-3 (IL-3)	Granulocyte, macrophage, eosinophil, megakaryocyte and erythroid colony formation
Interleukin-5 (IL-5)	B-cell differentiation and eosinophil regulation
Interleukin-6 (IL-6)	B-cell differentiation
Interleukin-7 (IL-7)	T-lymphocyte induction
Interleukin-11 (IL-11)	Stimulation of megakaryocytes and plasmacytoma cell lines
Leukemia inhibitory factor (LIF)	Differentiation and suppression of clonogenicity of leukemic cells
Macrophage-colony stimulating factor (M-CSF)	Macrophage colony stimulation
Stem cell factor (SCF)	Proliferation of mast cells and stem cells
Thrombopoietin (TPO)	Regulation of platelet production; stimulation of megakaryocytes with IL-3 and SCF

Two models were proposed to define the role of growth factors in hematopoietic differentiation.

• Instructive model assigns a direct role to cytokines in cell differentiation; cell fate is determined predominantly by the type of growth factor acting on the cell²
• Stochastic model suggests a pre-determined program for cell differentiation; growth factors are required specifically for survival and proliferation of committed progenitor cells³

Both models are based on evidence that growth factors control survival and proliferation of hematopoietic lineages and also transduce a genuine lineage-determining signal in hematopoiesis.¹ The future studies focusing on elucidation of the unique role of growth factors in a particular situation and/or microenvironment in various disease situations they may prove to be of critical clinical value.

Figure 1. Hematopoietic cytokines stimulate hematopoietic cells to differentiate into principle types of blood cells.

Adapted from Hematopoietic Cytokines by Jennifer Fries, BioFiles 2009, 4.5, 8.

References

1. Metcalf D. 2008. Hematopoietic cytokines. 111(2):485-491. https://doi.org/10.1182/blood-2007-03-079681

2. Borzillo GV, Ashmun RA, Sherr CJ. 1990. Macrophage lineage switching of murine early pre-B lymphoid cells expressing transduced fms genes.. Mol. Cell. Biol.. 10(6):2703-2714. https://doi.org/10.1128/mcb.10.6.2703

3. Till JE, McCulloch EA, Siminovitch L. 1964. A STOCHASTIC MODEL OF STEM CELL PROLIFERATION, BASED ON THE GROWTH OF SPLEEN COLONY-FORMING CELLS. Proceedings of the National Academy of Sciences. 51(1):29-36. https://doi.org/10.1073/pnas.51.1.29