Tumor necrosis factor has positive and negative self regulatory feed back cycles centered around cAMP

This paper reviews data that allow recognition of, (1) two opposing intracellular chains of events occurring subsequent to an increase in tumor necrosis factor, TNF, and (2) that these two chains have opposing effects on intracellular cyclic adenosine monophosphate, cAMP. The two chains - attenuation cycle, where TNF results in prostaglandin E mediated increased cAMP and, consequent to this, suppression of TNF levels; and an amplification cycle, where increased TNF increases intracellular cyclic adenosine phosphodiesterase, lowering cAMP, thereby raising TNF levels further. TNF is a central mediator in several inflammatory diseases. Understanding TNF control systems will allow better delineation of pathophysiology and clinical care. (C) 2000 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved.