HMGB-1, a DNA-binding protein with cytokine activity, induces brain TNF and IL-6 production, and mediates anorexia and taste aversion.

Abstract

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.

• Authors: Davide Agnello, Haichao Wang, Huan Yang, Kevin J Tracey, Pietro Ghezzi
• Journal: Cytokine (Cytokine) Vol. 18 Issue 4 Pg. 231-6 (May 21 2002) ISSN: 1043-4666 [Print] England
• PMID: 12126646 (Publication Type: Journal Article)

Chemical References

• Cytokines
• HMGB1 Protein
• Interleukin-6
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Anorexia
• Appetite
• Body Weight
• Brain (metabolism)
• Cerebral Ventricles (metabolism)
• Cytokines (metabolism)
• Eating
• HMGB1 Protein (metabolism, physiology)
• Interleukin-6 (metabolism)
• Male
• Mice
• Mice, Inbred C3H
• Taste
• Time Factors
• Tumor Necrosis Factor-alpha (metabolism)