Inhibition of growth by pro-inflammatory cytokines: an integrated view.
In response to antigenic stimuli, a variety of cells, including activated macrophages, secrete cytokines that are responsible for altering the host's metabolism. Three of these cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin-1 [IL-1], and interleukin-6 [IL-6]) have profound behavioral, neuroendocrine, and metabolic effects. There is evidence that cytokines and their cognate receptors are present in the neuroendocrine system and brain. Moreover, in laboratory animal species, IL-1, IL-6, and TNF-alpha have been found to modulate intermediary metabolism of carbohydrate, fat, and protein substrates, regulate hypothalamic-pituitary outflow, and act in the brain to reduce food intake. Finally, many of the systemic acute-phase responses to inflammatory stimuli such as lipopolysaccharide are inhibited by treatment with cytokine receptor antagonists. In short, many findings converge to suggest that a major component of the growth inhibition observed in immunologically challenged animals is mediated by pro-inflammatory cytokines. The goal of this article is to provide an integrated view of how cytokines act systemically on disparate tissues to alter growth.
Johnson
R W
RW
Department of Animal Sciences, University of Illinois, Urbana 61801, USA.
D000210:Acute-Phase Reaction; D000818:Animals; D001806:Blood Urea Nitrogen; D001921:Brain / Q000502:physiology; D001923:Brain Chemistry; D016207:Cytokines / Q000032:analysis / Q000097:blood / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D006128:Growth / Q000502:physiology*; D006854:Hydrocortisone / Q000032:analysis / Q000097:blood / Q000502:physiology; D007107:Immune System / Q000502:physiology; D007375:Interleukin-1 / Q000032:analysis / Q000097:blood / Q000502:physiology; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood / Q000502:physiology; D009490:Neurosecretory Systems / Q000737:chemistry / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism / Q000502:physiology
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D006854:Hydrocortisone