Bile acids in physico-chemical host defence

Abstract

The discovery of the physico-chemical host defence is closely connected with the endotoxin research. It is well known that the toxic effects of endotoxins under experimental conditions can be induced only when they are administered parenterally. However, in naturally occurring entero-endotoxemic diseases (e.g. septic and various shocks, etc.), the endotoxin is absorbed from the intestinal tract. The cause and mode of translocation have been unknown. The generally used experimental shock models differ from natural diseases only in the mode by which endotoxin enters the blood circulation. If the common bile duct of rats was chronically canulated (bile-deprived animals) orally administered endotoxin was absorbed from the intestinal tract into blood circulation and provoked endotoxin shock. This translocation of endotoxins and the consequent shock can be prevented by sodium deoxycholate or natural biles. The bile acids split the endotoxin macromolecule into atoxic fragments. A similar detoxifying detergent action plays a significant role in host defence against infectious agents with outer lipoprotein structure (e.g. so-called 'big' viruses). This defence mechanism of macroorganisms based on the detergent activity of bile acids (end-products of the cholesterol metabolism) is called as physico-chemical defence system. Therefore, bile deficiency and the consequent endotoxemia are important components in the pathogenesis of certain diseases (e.g. sepsis, intestinal syndrome of radiation disease, hepato-renal syndrome, parvovirus infection, herpes, psoriasis, atherosclerosis, etc.). Bile acids may be used for the prevention and/or therapy of the above mentioned clinical conditions.