Cytokines,Metabolism,and Nutrition: Overview

Abstract

Just a few years ago, the mechanisms underlying the metabolic alterations associated with infection and inflammation were rather mysterious. Then, a series of startling discoveries suggested that these pathways would soon be unraveled with a clarity that might permit targeted interventions. This was based on extensive information derived from the in vitro study of certain peptide mediators released during infection and inflammation, particularly interleukin (IL)-l and tumor necrosis factor, and more limited in vivo investigations in certain animals concerning their effects on host metabolism. These data are reviewed in the paper by Bistrian and colleagues in this symposium.

While the view that these two cytokines are the signals to reorganize metabolic priorities during infection and inflammation remains the most likely mechanism for these events, more recent studies have identified many more mediators with overlapping properties and both up- and down-regulatory controls. In addition, it has been found that responses in vivo may not parallel those obtained in vitro, as reviewed in the paper by Grunfeld and Feingold in this symposium, which complicates the interpretation of the earlier data. While the two initially described metabolic regulators (IL-1 and tumor necrosis factor) continued to hold center stage as the best and most likely candidates for the role of conductor of the metabolic response to infection and inflammation, it is still too early to be absolutely certain of even this. The paper by Dinarello in this symposium suggests some of the technical and biological reasons for this. For example, he discusses the many pitfalls in the accurate assay of cyotkines and how readily un- physiological experimental conditions can lead to spurious results. In addition, Dinarello demonstrates the clear separation of transcription from translation of the IL-1 gene and he discusses the difference in the nature of the signals required for these two steps in the ctyokine pathway. The strong implication is that studies that do not assess both steps in gene activation may lead to inappropriate conclusions, and that in vitro studies that do not select the correct stimuli for cytokine pathway activation may lead to incorrect assumptions on in vivo events.