Methods of inhibiting HMGB1 release by a mammalian cell are provided. The methods comprise treating the cell with sufficient fetuin to inhibit HMGB1 release. Methods of inhibiting an inflammatory cytokine cascade in a mammal are also provided. These methods comprise administering sufficient fetuin to the mammal to inhibit HMGB1 release in the mammal. Also provided are methods of treating a condition in a mammal characterized by an inflammatory cytokine cascade. These methods comprise administering sufficient fetuin to the mammal to inhibit HMGB1 release in the mammal.