Role of endotoxins and bile acids in the pathogenesis of septic circulatory shock

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ABSTRACT:

It is well known that the bacterial endotoxins play an important role in he pathogenesis of irreversible septic (surgical) shock. The endotoxins can initiate the production of noxious mediators (e.g. cytokines, prostaglandins etc.) and these factors are the elicitors of the endotoxic shock. It has long been also known that the toxic effects of endotoxic lipopolysaccharides (LPS) under experimental conditions can be induced only when they are administered parenterally. However, in naturaEy occurring enteroendotoxemic diseases (e.g. various shocks, etc.), the LPS absorb from the intestinal tract. The parenterally (intraperitoneal or intravenous) administered LPS induces prostration, diarrhea, and circulatoiy disturbances indistinguishable from those observed in natural diseases. At autopsy, animals killed by parenterally administered LPS show changes that are similar to the natural diseases of species sensitive to LPS (intestinal edema, hemorrhages, etc.). The generally used experimental models differ from natural diseases only in the mode by which LPS enters the blood circulation (2,7). Given orally, LPS has no effect, even on sensitive species, when given in doses from 500 to 3.000 time the minimal parenterally lethal dosage.lt is also ineffective when the intestinal mucosa of the experimental animal has been damaged by various interventions. There is no in vitro evidence of the existence of some intestinal enzyme which could specifically decompose the LPS and thus produce resistance to the orally administered material. As a matter of fact, orally administered LPS can be recovered essentially unaltered from the gastrointestinal tract by means of the phenol-water extraction procedure. Even in a lead acetate sensitizing procedure, orally administered LPS has not been found to be toxic. The way in which LPS reaches the circulation from the intestinal tract in natural endotoxic diseases remains a mystery.

Source: National Research Institute for Radiobiology and Radiohygiene, Budapest – 1997