Disease relevance of Shwartzman Phenomenon

• We chose the dermal necrosis of the local Shwartzman phenomenon and the renal cortical necrosis of the general Shwartzman phenomenon as assays because these are the hallmarks of meningococcemia, and because meningococcal lipopolysaccharide (LPS) is a uniquely potent cause of dermal purpura and necrosis [1].
• However, priming with high doses of LPS caused mortality of severe combined immunodeficiency, NKT cell-deficient, and CD1-deficient mice, indicating a major contribution of NKT cells to the Shwartzman reaction elicited by low doses of LPS, whereas at higher doses of LPS NK cells play a prominent role [2].
• Interleukin-10 is a central regulator of the response to LPS in murine models of endotoxic shock and the Shwartzman reaction but not endotoxin tolerance [3].
• BACKGROUND AND PURPOSE: We earlier reported that risk factors for stroke prepare brain stem tissue for a modified Shwartzman reaction, including the development of ischemia and hemorrhage and the production of tumor necrosis factor-alpha, after a provocative dose of lipopolysaccharide [4].
• Compound 516 exhibited considerably weaker pyrogenic and leukopenic activity than compound 506, and it scarcely prepared rabbit skin for the Shwartzman reaction and lacked lethal toxicity on chicken embryos, although its lethal toxicity in galactosamine-loaded mice was as strong as that of compound 506 [5].

High impact information on Shwartzman Phenomenon

• Using the Shwartzman reaction, we observed that nicotine (2 mg/kg) and the novel cholinergic agent CAP55 (12 mg/kg) inhibit endothelial cell adhesion molecule expression [6].
• The generalized Shwartzman reaction in mice which had been primed and challenged with lipopolysaccharide (LPS) depends on interleukin (IL)-12-induced interferon (IFN)-gamma production at the priming stage [2].
• Interleukin 12, interferon gamma, and tumor necrosis factor alpha are the key cytokines of the generalized Shwartzman reaction [7].
• A study of the large heparin requirements in the generalized Shwartzman reaction [8].
• Cutting edge: IL-15 costimulates the generalized Shwartzman reaction and innate immune IFN-gamma production in vivo [9].

Chemical compound and disease context of Shwartzman Phenomenon

• The Shwartzman reaction is elicited by two injections of lipopolysaccharide (LPS) in mice [7].
• The effects of indomethacin on the generalized shwartzman reaction [10].
• Intradermal injection of epsilon-aminocaproic acid failed to prepare for the local Shwartzman reaction [11].
• Effect of cyclosporin on generalized Shwartzman reaction in diabetic rats [12].
• The generalized Shwartzman reaction (GSR) was produced by a single injection of endotoxin in male rats pretreated with catechol-o-methyltransferase (COMT) inhibitors (tropolone, pyrogallol) [13].

Biological context of Shwartzman Phenomenon

• (+/-)-Thalidomide, (-)-thalidomide, (+)-thalidomide and dexamethasone inhibited the increase of vascular permeability in the local Shwartzman reaction [14].

Anatomical context of Shwartzman Phenomenon

• Such IFN-gamma may then in turn sensitize macrophages to elicit the Shwartzman reaction following a subsequent LPS challenge [9].
• Our findings show that IFN-gamma produced by NK1+ alphabeta T cells is essential for the IL-12 priming of the Shwartzman reaction, and the autoreactivity of NK1+ alphabeta T cells in the liver is involved in the hepatic disorders that are sometimes caused by IL-12, LPS, or the generalized Shwartzman reaction [15].
• It was suggested that ICAM-1 expression on vascular endothelial cells might be involved in systemic vascular injuries of the generalized Shwartzman reaction, and that it might be regulated by gamma interferon [16].
• The effects of ulinastatin (UST) and methyl prednisolone (MPS) on endotoxin induced shock were compared by the criterion of microcirculation dynamics in rat mesenterium and plasma phospholipase A2 (PLA2) activity in modified Shwartzman reaction model [17].

Gene context of Shwartzman Phenomenon

• IL-12 was found to be the main inductor of IFN-gamma during the lethal Shwartzman reaction [18].
• The reported findings implicate a synergism between IL-1 and TNF alpha in the induction of both the inflammatory reaction (preceding the Shwartzman reaction) and the thrombohemorrhagic component of the Shwartzman reaction proper [19].
• Tissue plasminogen activator therapy of glomerular thrombi in the Shwartzman reaction [20].
• Glomerular fibrinolytic activity was reduced following development of the generalized Shwartzman reaction but was normal in animals that received TPA five hours after the second injection of endotoxin [20].
• Sensitization to the generalized Shwartzman reaction by catechol-O-methyltransferase inhibitors [13].

Analytical, diagnostic and therapeutic context of Shwartzman Phenomenon

• In rabbits, passive immunization with anti-lipopolysaccharide (LPS) polyclonal antibodies prior to the intravenous (i.v.) injection of LPS inhibits the haemorrhagic necrotic lesion characteristic of the local Shwartzman reaction (an excellent localized in vivo correlate of the septic shock) [21].

References