Lipopolysaccharide (LPS) is toxic to the host and will only be released when the bacteria die and dissolve or the bacterial cells are destroyed by artificial methods, also known as endotoxin. When LPS acts on other biological cells such as humans or animals, it will show a variety of biological activities and functions.
Small doses of endotoxin can activate B lymphocytes to produce polyclonal antibodies, promote the development and maturation of T lymphocytes, activate NK cell activity, activate macrophages, and enhance their phagocytosis and digestion capabilities. And synthesize and secrete interferon, tumor necrosis factor, colony-stimulating factor, interleukin, and other cytokines to regulate the immune response. In addition, endotoxin can activate complement through alternative pathways and exert a series of biological effects of complement activation. Therefore, endotoxin can enhance the body's non-specific immunity through the above mechanism.
Small doses of endotoxin can induce endotoxin tolerance, which is mainly the result of changes in the expression and properties of related receptors. For example, the expression of TLR4 is down-regulated and the activity of transcriptional regulators is changed. In the composition of the nuclear factor NF-κB complex, p65 is increased and p50 is decreased, which affects the translocation of nuclear factor into the nucleus and reduces the expression of its governing genes.
Endotoxin can activate monocytes-macrophages, neutrophils, endothelial cells, etc. in body tissues, among which monocytes-macrophages secrete a large number of cytokines such as TNF and colony-stimulating factor, through receptor signal transduction pathway to induce tumor cell necrosis and apoptosis. The immune cell effect is significantly enhanced after being stimulated by cytokines, which improves the ability to recognize and kill tumor cells and exerts an anti-tumor effect.
Figure 1. The diagram illustrating the effects and mechanisms of inhibiting the early response cytokines on inhibiting endotoxin-induced lung injury. (Chen K Y, et al., 2022)
Endotoxin is injected into the body together with other soluble particulate antigens, which can significantly increase the titer of the latter stimulating the body to produce antibodies. This is because endotoxin can activate immunocompetent cells and endothelial cells, epithelial cells, etc., so endotoxin has an immune adjuvant effect.
Endotoxin can enhance the body's ability to resist the destructive effects of X-rays against infection. For example, after the mice were irradiated with 6Gy X-rays, the bactericidal factors in the serum disappeared rapidly. At this time, bacterial endotoxin was injected immediately, and the bactericidal factors were found to return to normal levels within a few hours, which lasted for about one week. A few hours after the injection of endotoxin, an increase in non-specific immunity can occur. Therefore, using a small dose of endotoxin to stimulate the body to resist radiation is a clue worth exploring.
Endotoxin induces the enhancement of integrin expression, and through the action of integrin and intercellular adhesion molecules, leukocytes adhere to blood vessels, prompting leukocytes to migrate to inflammatory sites and exert immune effects, such as phagocytosis of pathogens and secretion of various cytokines. Biological mediators such as chemical factors, and through these mediators, have a variety of beneficial and unfavorable biological effects on the body. At the same time, it destroys the integrity of the basement membrane of endothelial cells, activates the coagulation system, and induces endothelial cell apoptosis and other effects.
Endotoxins can cause fever in humans and animals. The mechanism of endotoxin-induced fever is mainly that endotoxin acts on monocytes and macrophages in blood and tissues to secrete TNF-α, IL-1, IL-6 and other biological mediators, which act on the temperature setting point (set point) of the thermoregulatory center of the hypothalamus raises the set point (temperature threshold). Because bacterial lipopolysaccharides are ubiquitous, some biological products often have a fever reaction after injection into the human body, which may be related to endotoxin contamination.
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