INHIBITION OF GROWTH BY PRO-INFLAMMATORY CYTOKINES - AN INTEGRATED VIEW

In response to antigenic stimuli, a variety of cells, including activa ted macrophages, secrete cytokines that are responsible for altering t he host's metabolism. Three of these cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin-1 [IL-1], and interleukin-6 [IL-6]) hav e profound behavioral, neuroendocrine, and metabolic effects. There is evidence that cytokines and their cognate receptors are present in th e neuroendocrine system and brain. Moreover, in laboratory animal spec ies, IL-1, IL-6, and TNF-a have been found to modulate intermediary me tabolism of carbohydrate, fat, and protein substrates, regulate hypoth alamic-pituitary outflow, and act in the brain to reduce food intake. Finally, many of the systemic acute-phase responses to inflammatory st imuli such as lipopolysaccharide are inhibited by treatment with cytok ine receptor antagonists. In short, many findings converge to suggest that a major component of the growth inhibition observed in immunologi cally challenged animals is mediated by pro-inflammatory cytokines. Th e goal of this article is to provide an integrated view of how cytokin es act systemically on disparate tissues to alter growth.