REGULATION OF TUMOR-NECROSIS-FACTOR PRODUCTION BY MONOCYTE-MACROPHAGES AND LYMPHOCYTES

TNF, a cytokine originally considered the product of only one cell type, the monocyte-macrophages, is now known to be produced by cells of many different lineages, with mechanisms of stimulation typical for each cell type analyzed. The fact that many different cell types can produce a cytokine such as TNF that has a very large spectrum of biologic functions on almost any target cell type is suprising. The functions of the cell types that produce TNF, e.g. monocyte-macrophages, neutrophils, T and B cells, are profoundly affected by TNF itself. Furthermore, TNF is able to induce its own gene, making these autocrine circuits even more complex. Because TNF has important systemic effects and it has been shown to be in vivo a major and necessary pathogenetic factor in situations such as endotoxin shock, graft-versus-host disease, and hypothermia induced by anti-T cell antibodies, it is clear that its production and its localization should be highly regulated in vivo and that our understanding of the regulation of TNF production based almost exclusively on in vitro observation is still very limited. Further analysis of the fine mechanisms of regulation of TNF production in vivo is required for a better under standing of the role of TNF in physiological and pathological conditions. © 1991 Humana Press Inc.