Download - PDF

The physiological role of endotoxin in humans is multifaceted and dose-dependent. We now know that endotoxins only exert their effects when released from the surface of Gram-negative bacteria. This can happen when the bacterium dies or when it starts to multiply. Normally, millions of Gram-negative bacteria live in the mammalian body and do not cause any health problems. In pathological cases, endotoxemia occurs as a result of large amounts of endotoxin entering the bloodstream, which can cause trauma and shock.

Endotoxins act mainly through macrophages. These cells, which play a protective role, normally absorb and break down substances harmful to the body. Endotoxin (LPS) released by living or dead bacteria binds to lipopolysaccharide binding protein (LPB) in the blood. The LPB-LPS complex binds to the CD14 receptor, a process that results in macrophage activation. Activated macrophages induce the formation of various molecules, mainly cytokinins (e.g. IL-1, IL-6, TNF-α, IFN-g, etc.), which are ultimately released into the circulatory system and activate the immune system through various mechanisms.

The body's defence mechanism becomes overwhelmed by the increased amount of endotoxin entering the bloodstream, and the immune system "overreacts" to the threat, which can lead to tissue destruction, endotoxic shock and eventually death.

Sepsis is another manifestation of bacterial infection. Sepsis occurs when pathogenic bacteria from a purulent nodule overwhelm the defence mechanism and spread to different parts of the body, and together with endotoxins, enter the bloodstream, leading to the symptoms of sepsis.

Sepsis and endotoxemia are still the leading causes of death in non-cardiac surgery. Between 35-45% of patients with sepsis die, despite modern hospital care. It is estimated that in the US alone, 300,000 people develop sepsis each year and 100,000 of these die.

However, preventing bacterial contamination, including endotoxin contamination, is not only in the health interest but also in the business interest. An important quality requirement for injectable drugs, surgical instruments, fluids and dialysis tubes is that they are sterile and endotoxin-free. Manufacturing companies are forced to spend considerable sums to ensure that these products are truly free of endotoxin contamination. Consequently, the importance of determining endotoxin contamination is increasing. The determination of endotoxin contamination is a critical parameter in pharmaceutical and biotechnological processes as well as in healthcare services (e.g. monitoring of haemodialysis systems).

Source : http://www.opulus.hu/microcontamination/endotoxin/effects/effects.asp