Mechanisms that regulate the production and effects of tumor necrosis factor-alpha

Macrophage-derived tumor necrosis factor (TNF) is increasingly being recognized as an important monokine possessing multifunctional activities. Current evidence has demonstrated that TNF can induce a number of pleomorphic effects in both physiological and immunological systems. Historically, the biological effects and nomenclature of TNF centered around the induction of hemorrhagic necrosis of specific solid murine tumors. This effected function has been greatly expanded upon, and TNF is now recognized as an important peptide mediator involved in various facets of cell activation. This is exemplified by the central role that TNF plays in endotoxemia, shock and multiple organ failure syndromes. Although TNF has been incriminated as the molecular signal mediating number of pathophysiological derangements, the regulatory mechanisms that control TNF expression at the cellular and molecular levels, as well as the modulation of the in vivo activity of preformed TNF, has not been full addressed. In this review, a detailed description of the mechanisms that regulate the production and effects of TNF is presented.