Colony-stimulating factors CSFs

The biosynthesis, molecular properties and receptors for the major colony-stimulating factors, as well as their role in haematopoiesis, is described in Chapter 2. The following section describes the role of G- and GM-CSF in the modulation of the function of mature, circulating neutrophils. 

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Cytokines and Immunophilins. A large number of inflammatory mediators and related proteins including the cytokines, colony stimulating factors (CSFs), interferons (IFNs), tumor necrosis factors (TNFs), growth factors (see Growth regulators), neurotrophic factors, and immunophilins are found in the mammalian CNS and appear to play a significant role in CNS function both in development and in aspects of brain homeostasis (40—43). 

Park, L.S., Friend, D., Gillis, S., and Urdal, D.L. (1986) Characterization of the cell surface receptor for a multi-lineage colony-stimulating factor (CSF-2a)./. Biol. Chem. 261, 205-210. 

It overcomes the problem of source availability. Many proteins of therapeutic potential are produced naturally in the body in minute quantities. Examples include interferons (Chapter 8), interleukins (Chapter 9) and colony-stimulating factors (CSFs Chapter 10). This rendered impractical their direct extraction from native source material in quantities sufficient to meet likely clinical demand. Recombinant production (Chapters 3 and 5) allows the manufacture of any protein in whatever quantity it is required. 

Interleukins (IL-l-IL-13 have now been characterised) colony-stimulating factors (CSFs), such as granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF) and macrophage CSF (M-CSF) ... 

R. J. Tushinski and E. R. Stanley, The regulation of mononuclear phagocyte entry into S phase by the colony stimulating factor CSF-1, J.Cell.Physiol. 122, 221-228 (1985). 

D. A. Hume, P. Pavli, R. E. Donahue, and I. J. Fidler, The effect of human recombinant macrophage colony-stimulating factor (CSF-1) on the murine mononuclear phagocyte system in vivo, J.Immunol. 141, 3405-3409 (1988). 

Erythropoietin is a peptide hormone that is formed predominantly by the kidneys, but also by the liver. Together with other factors known as colony-stimulating factors" (CSF see p.392), it regulates the differentiation of stem cells in the bone marrow. 

There is an extremely large number of cytokines only the most important representatives are listed opposite. The cytokines include interleukins (IL), lymphokines, monokines, chemokines, interferons (IFN), and colony-stimulating factors (CSF). Via interleukins, immune cells stimulate the proliferation and activity of other immune cells (see p. 294). Interferons are used medically in the treatment of viral infections and other diseases. 

Initial classification of some cytokines was also undertaken on the basis of the specific biological activity by which the cytokine was first discovered, e.g. TNF exhibited cytotoxic effects on some cancer cell lines, colony stimulating factors (CSFs) promoted the growth in vitro of various leukocytes in clumps or colonies. This, too, proved an unsatisfactory classification mechanism, as it was subsequently shown that most cytokines display a range of biological... 

Table 5.1. Many cell types are capable of producing a whole range of interleukins. T lymphocytes are capable of producing all the ILs, with the possible exception of IL-7 and IL-15. Many cell types producing multiple ILs can also produce additional cytokines, e.g. both macrophages and fibroblasts are capable of producing several ILs, colony stimulating factors (CSFs) and platelet-derived growth factor (PDGF)...

Debrix I, Madelaine I, Grenet N, Roux D, Bardin C, Le Mercier F et al. Impact of ASCO guidelines for the use of hematopoietic colony stimulating factors (CSFs) survey results of fifteen Paris university hospitals. Pharm World Sci 1999 21 270-1. 

The first group of cytokines discovered, the interferons (IFNs), were followed by the colony-stimulating factors (CSFs, discussed in Chapter 33). The latter regulate the proliferation and differentiation of bone marrow progenitor cells. Most of the more recently discovered cytokines have been classified as interleukins (ILs) and numbered in the order of their discovery. Cytokines are produced using gene cloning techniques. 

Stimulation of hematopoeiesis (IL-3, IL-7), colony-stimulating factors (CSF see also Chapter 32). 

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