The inhibition of HMGB1 also has been an important topic for those seeking to ameliorate injury by decreasing the level of HMGB1 release. A variety of pharmacologic agents have been studied for their potential to inhibit release of HMGB1; however, a full discussion of pharmacologic inhibition of HMGB1 is beyond the scope of this paper. It is worth noting, though, that HSP72, an endogenous molecule that has itself been indicted as an alarmin, has been demonstrated to inhibit HMGB1 release. Originally, it was demonstrated that brief heat shock resulted in decreased HMGB1 release from LPS-stimulated macrophages, but no specific pathway was identified (32) . Recently, HSP72 overexpression has been shown to inhibit HMGB1 release from macrophages in response to LPS, TNFα, or oxidative stress (hydrogen peroxide). This inhibition appears to be due to intranuclear interactions between HSP72 and HMGB1 (44, 45) .