Recombinant human TNF induces production of granulocyte-monocyte colony-stimulating factor

Tumour necrosis factor (TNF) is synthesized by macrophages exposed to endotoxin¹. It produces haemorrhagic necrosis of a variety of tumours in mice and is cytostatic or cytocidal against various transformed cell lines in vitro, but viability of normal human or rodent cells is unaffected ^2-4. The role of TNF is unlikely to be restricted to the rejection of tumours. Colony-stimulating factors (CSFs) are required for survival, proliferation and differentiation of haematopoietic progenitor cells. The haematopoietic growth factor known as granulocyte-monocyte colony-stimulating factor (GM-CSF) has the ability to stimulate proliferation and differentiation of normal granulocyte-monocyte and eosinophil stem cells and enhance the proliferation of pluripotent, megakaryocyte and erythroid stem cells ⁵. In addition, GM-CSF stimulates a variety of functional activities in mature granulocytes and macrophages, for example inhibition of migration, phagocytosis of microbes, oxidative metabolism, and antibody-dependent cytotoxic killing of tumour cells^5-7. We show here that TNF markedly stimulates production of GM-CSF messenger RNA and protein in normal human lung fibroblasts and vascular endothelial cells, and in cells of several malignant tissues.