title: Signals generating anorexia during acute illness.
abstract: Anorexia is part of the body's acute-phase response to illness. Microbial products such as lipopolysaccharides (LPS), which are also commonly used to model acute illness, trigger the acute-phase response and cause anorexia mainly through pro-inflammatory cytokines. LPS stimulate cytokine production through the cell-surface structural molecule CD14 and toll-like receptor-4. Cytokines ultimately change neural activity in brain areas controlling food intake and energy balance. The blood-brain barrier endothelial cells (BBB EC) are an important site of cytokine action in this context. BBB EC and perivascular cells (microglia and macrophages) form a complex regulatory interface that modulates neuronal activity by the release of messengers (e.g. PG, NO) in response to peripheral challenges. Serotonergic neurons originating in the raphe nuclei and glucagon-like peptide-1-expressing neurons in the hindbrain may be among the targets of these messengers, because serotonin (5-HT), acting through the 5-HT2C receptor, and glucagon-like peptide-1 have recently emerged as neurochemical mediators of LPS anorexia. The central melanocortin system, which is a downstream target of serotonergic neurons, also appears to be involved in mediation of LPS anorexia. Interestingly, LPS also reduce orexin expression and the activity of orexin neurons in the lateral hypothalamic area of fasted mice. As the eating-stimulatory properties of orexin are apparently related to arousal, the inhibitory effect of LPS on orexin neurons might be involved in LPS-induced inactivity and anorexia. In summary, the immune signalling pathways of LPS-induced, and presumably acute illness-induced, anorexia converge on central neural signalling systems that control food intake and energy balance in healthy individuals.
authors.affiliation: Physiology and Behaviour Group, Institute of Animal Sciences, ETH Zurich, Schwerzenbach, Switzerland. wolfgang-langhans@ethz.ch
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Langhans
mesh_terms: D000210:Acute-Phase Reaction / Q000150:complications; D000818:Animals; D000855:Anorexia / Q000209:etiology*; D001921:Brain / Q000378:metabolism*; D016638:Critical Illness; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D008070:Lipopolysaccharides; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides