Endotoxin is not only the main pathogenic factor of Gram-negative bacterial infection but also an important factor that still endangers the health of animals and humans. Therefore, the research on anti-endotoxin inhibition measures is particularly important. At present, a series of anti-endotoxin molecules have been studied, including endotoxin antagonists, endotoxin-binding reagents, vaccines, and antibiotics. Some endotoxin-neutralizing agents under investigation are recombinant high-density lipoprotein (HDL) polymyxin binders, lipid A anti-agents, anti-endotoxin antibodies, and neutralizing proteins. The action of endotoxin inhibitors and endotoxin is a reversible reaction, which does not destroy endotoxin. When these inhibitors are removed or destroyed by various methods, the activity of endotoxin can be completely restored.
Figure 1. The location of the lipopolysaccharide (endotoxin) molecule in the cell wall of Gram negative bacteria. (Hurley J C, 2013)
The extracellular neutralization of IgG and IgM anti-lipopolysaccharide monoclonal antibodies has a certain anti-endotoxin effect, but it has no obvious effect on reducing the mortality rate, and monoclonal antibodies are expensive. Therefore, looking for new anti-endotoxin drugs has become the top priority of the world's medical community.
Pentoxifylline can inhibit endotoxin-induced TNF synthesis, so it will be beneficial to treat patients with clinical endotoxemia with pentoxifylline.
Dexamethasone is a typical representative of this class of drugs, and phospholipase A2 is a key enzyme in the inflammatory response, which is considered to play an important role in intestinal inflammatory diseases. Endotoxin can mediate the synthesis of intestinal phospholipase A2, while glucocorticoids can inhibit its production, thereby reducing the damage of endotoxin to the gastrointestinal tract.
The drug is used for anti-shock, and its mechanism of action is mainly due to its vasodilation effect. As a result of the drug's clinical use, it is believed to have a good anti-endotoxic shock effect.
The body can resist intestinal bacterial infection, suggesting that the body has the function of destroying endotoxin and corresponding microorganisms. However, no consensus has been reached on the main detoxification site of endotoxin in the body and the mechanism of the body's resistance to the toxic effect of endotoxin, but the irreversible enzymatic reaction is more inclined to the detoxification mechanism. Bactericidal/penetration-enhancing protein (BPI), derived from neutrophils, counteracts the toxic effect of endotoxin in circulation by competing with serum proteopolysaccharide-binding protein (LBP) for binding lipopolysaccharide. Anti-lipopolysaccharide antibodies (IgM) bind and inactivate heterologous LPS to which the host has been exposed. Among other things, high-density lipoprotein (HDL) metabolizes and clears LPS.
The liver is the main organ for the body to remove endotoxins. Regardless of whether endotoxins come from portal blood or systemic circulation, most endotoxins are detoxified by the liver. The mechanism includes three aspects:
Endotoxin inhibitors in plasma come in multiple types, and they are not composed of only one substance.
HDL is considered to be a carrier of endotoxin in the circulation, which can transport endotoxin to clearing organs, and endotoxin bound to high-density lipoprotein has various biological activities.
Previous studies have shown that endotoxin is mainly cleared and inactivated in the mononuclear phagocyte system, especially in the liver. Some experiments have also shown that the endotoxin content of blood entering the lungs of normal rabbits is significantly higher than that of blood leaving the lungs, indicating that under normal conditions The lungs have the function of removing endotoxins from the circulating blood.
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