The appraisal of the contribution of glucocorticoid hormones to the pathogenesis of various forms of stress' and shock has got a long and often contradictory history. Research in the last few years has provided new data on the role of the steroid hormone receptors, the cytokine cascade and macrophages in experimental septic and endotoxic shock. the glucocorticoid antagonist RU 38486 (Roussel Uclaf, France) sensitized experimental animals to the mortal effects induced by either bacterial endotoxin or septic shock secondary to septic peritonitis induced by coecal ligation and puncture, which is somewhat comparable to the human pathology. We have shown both in vivo, in experimental animals, and in vitro, in tissue culture, that RU 38486 significantly increases the synthesis and toxicity of tumour necrosis factor (TNF), which is one of the most important mediators in endotoxin and septic shock. Macrophages are the body's 'alarm' cells, and in severe injuries such as shock stares, the 'over'-activaiion of macrophages and the excessive release of macrophage-derived destructive and immunosuppressive products may contribute to the damage of organs and the development of multiple organ failure'. It has been reported earlier that rare earth metal salts, including gadolinium chloride (GdCl3), depress the reticuloendothelial activity, selectively blocking the function of the hepatic Kupffer cells. Several studies also indicate that GdCl3 suppresses a broad range of the Kupffer cell functions, such as the phagocytosis, the release of cytokines and immune recognition. These studies suggest that the inhibition of macrophage activation may lead to tolerance or resistance of the organism.
|Translated title of the contribution||Tolerance and hypersensitivity in experimental models|
|Number of pages||5|
|Journal||Lege Artis Medicinae|
|Publication status||Published - Oct 15 1997|
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