Cytokines at the research-clinical interface: potential applications.

Developments in the characterization of growth factors and the recognition of their potential for clinical use has advanced through a number of stages. The development of clonogenic haemopoietic colony assays in the 1960s led to the discovery of colony-stimulating activity in the conditioned medium produced by certain cell lines. This activity was then purified and the colony-stimulating factors were identified. With rapid progress in molecular biology techniques in the 1980s, many further growth factors were cloned and produced on an industrial scale. Although erythropoietin, interferons, G-CSF, GM-CSF and IL-2 were all introduced into clinical practice as single agents, cytokines have more recently been investigated for use either in combination, or sequentially. Clinical trials are currently in progress to examine the optimum combinations and timing of administration. Current clinical applications include optimization of methods for mobilization of peripheral blood progenitor cells and amelioration of cytopenias following chemotherapy and bone-marrow transplantation. In the future, cytokines will be employed to expand stem and progenitor cells ex vivo, to improve gene transduction strategies, possibly to protect the gastrointestinal epithelium and as immunomodulators, both in vivo and in vitro. This review will focus on recently characterized growth factors including c-kit ligand/stem cell factor, flt3 ligand, c-mpl ligand/thrombopoietin and interleukins-11, 4, 7, 10, 12 and 13.