In conclusion, one may suggest that a physico-chemical defence mechanism, which is based on the detergent action of bile acids, provide the body with a general defence, which is not limited to bacterial endotoxins, but is also effective against other agents (e.g., viruses) that possess lipoprotein or lipid structures. This novel mechanism may be added to the known defence mechanisms, which are based on bile acids produced in the liver and present in the enterohepatic circulation. It is interesting to note in this respect that bile acids are the most important products of cholesterol metabolism, which are reusable end products that affect the production of steroid hormones (by the adrenal gland and gonads). It is possible that bile acids play a role also in the pathophysiology of endocrine and reproductive abnormalities, which remains to be elucidated
It is possible that deficient bile production or secretion leads to the absorption of minute amounts of endotoxin, which may play a role in the induction of atherosclerosis. We showed in cholesterol-treated rabbits that endotoxin significantly increases the development of atherosclerosis . Recently several authors recognized his fact [49-60]. Partial or temporary bile acid deficiency may occur for several reasons: CCK deficiency, disturbance of bile secretion and deficient bile production due to liver damage, leading to endotoxin absorption. In turn, the absorbed endotoxin will act on sessile phagocytes fixed to the wall of blood vessels according to known pathways (e.g., endotoxin-binding protein and CD14 endotoxin receptor), which leads to the production of cytokines and other biologically active materials. These mediators, in conjunction with elevated cholesterol levels, could precipitate and initiate plaque formation. On this basis one may suggest that the systematic investigation of bile production and secretion from a young age and correction of deficiencies would decrease the development of atherosclerosis and the development of related diseases.
It is clear from the facts presented here that bile acids and endotoxins play a significant role in many more pathological conditions than were reasonably anticipated. It is likely that further investigation of these questions and the application of experimental results to patients will lead to new approaches in clinical medicine.
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