SHWARTZMAN REACTION

The local and generalized Shwartzman reactions are models of thrombohemorrhagic skin necrosis and DIC, respectively. An intravenous preparatory injection of endotoxin followed by an intradermal injection of endotoxin 24 hours later elicits a thrombohemorrhagic lesion only at the site of intradermal injection of endotoxin in the local Shwartzman reaction. Two intravenous injections of endotoxin spaced 24 hours apart induce a systemic generalized Shwartzman reaction characterized by coagulopathy, petechial hemorrhages, microthrombi, and decreased circulating platelets similar to DIC. Of particular interest is the observation that thrombohemorrhagic lesions of the Shwartzman reaction only develop at sites of intradermal injections of endotoxin. Microthrombi composed of platelets and leukocytes only adhere or accumulate in dermal vessels after an intradermal injection of endotoxin. Prior to the endotoxin injection, biopsies of skin show normal vessels without microthrombi or significant inflammation. Since endothelial cells line the small vessels in the dermis, where a Shwartzman reaction appears to be initiated, it is likely that endothelial cells are important for initiating a local Shwartzman reaction. IL-1 and TNF can substitute for the intradermal injection of endotoxin in the local Shwartzman reaction, induce endothelial cells to become thrombogenic, and can induce the expression of cell adhesion molecules on endothelial cells making endothelial cells more sticky for leukocytes. These observations suggest that endothelial cells play a central role in the local Shwartzman reaction and may be important in understanding diseases associated with thrombohemorrhagic skin necrosis.