Therefore, alarmins ought to be able to precondition against later insults as well. Proof of principle of this concept has been demonstrated by HMGB1's ability to provide protection when administered as a precondition agent in hepatic IRI (126) . HMGB1 administration 1 h prior to the onset of injury results in a dose-dependent protection as evidenced by decreased circulating biochemical markers of liver damage as well as decreased serum TNFα and IL-6 levels.