HMG-1 rediscovered as a cytokine

High-mobility group-1 (HMG-1), an abundant, highly conserved cellular prote in, is widely known as a nuclear DNA-binding protein that stabilizes nucleo some formation, facilitates gene transcription, and regulates the activity of steroid hormone receptors. We discovered that HMG-1 is a late mediator o f delayed endotoxin lethality. When released by activated monocytes, it par ticipates in the development of lethality and it activates downstream cytok ine release. This review covers the general features of HMG-1 and its newly appreciated role as a cytokine.