Human granulocyte-macrophage colony-stimulating factor (GM-CSF): regulation of expression.

GM-CSF is a potent hematopoietic growth factor which exerts its effects on hematopoietic cell growth both in vivo and in vitro. In addition, GM-CSF has profound effects enhancing the functional activity of circulating effector cells. GM-CSF can be produced by a variety of cell types in response to immune stimuli; both T-cells and macrophages produce GM-CSF upon activation. Furthermore, activated macrophages secrete IL-1 and TNF, which can stimulate GM-CSF production by certain types of endothelial and fibroblast cells. This local production of GM-CSF could then act on circulating neutrophils, monocytes and eosinophils to enhance their functions in host defense. Thus, one can envision a paracrine system in which the production of GM-CSF is sensitive to immune stimulation, and as a result of GM-CSF production, effector cells are recruited and their activities enhanced (Figure 4). The role of GM-CSF and other CSFs and interleukins in the homeostatic control of hematopoiesis is the subject of intense investigation. Careful integration of molecular and biological studies should yield exciting new information about both the physiologic and therapeutic roles of GM-CSF.