HMGB-1, a DNA-binding protein with cytokine activity, induces brain TNF and IL-6 production, and mediates anorexia and taste aversion.
High-mobility group protein-1 (HMG-1 also termed HMGB-1), a DNA-binding protein, regulates gene transcription and stabilizes nucleosome formation. HMG-1 was recently implicated as a cytokine, because it is a late-acting mediator of endotoxin lethality that induces the release of pro-inflammatory cytokines from monocytes. Here it is shown that administration of HMG-1 into the cerebral ventricles decreases food intake (food intake=4.6g/mouse in controls vs 1.6g/mouse after 1 microg HMG-1 i.c.v.; P <0.05). Intracerebroventricular HMG-1 induced an increased in TNF and IL-6 expression in the brain, and mediated taste aversion with potencies equivalent to LPS. In a model of endotoxemia, passive immunization with anti-HMG-1 antibodies attenuated the development of hypophagia, indicating that HMG-1 is a mediator of sickness behaviour associated with endotoxemia.
Laboratory of Neuroimmunology, Mario Negri Institute for Pharmacological Research, 20157 Milano, Italy.
Davide
D
Agnello
Haichao
H
Wang
Huan
H
Yang
Kevin J
KJ
Tracey
Pietro
P
Ghezzi
D000818:Animals; D000855:Anorexia; D001066:Appetite; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004435:Eating; D024243:HMGB1 Protein / Q000378:metabolism / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D013649:Taste; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D016207:Cytokines; D024243:HMGB1 Protein; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha