Endotoxin was first described in 1892 by Richard Pfeiffer who made the observation that when the cholera organism (Vibrio Cholera) was killed, a poison was released that caused the same reaction as the live bacteria. The “inside toxin” was called endotoxin.

For the past one hundred years, endotoxin has been one of the most studied bacterial products. Not only does endotoxin elicit a strong direct response but they possess the ability to trigger and antagonize the action of other hormonal or chemical mediators.

"Endotoxins possess an instrinsic fascination that is nothing less than fabulous”

Ivan L. Bennett, 1964
 

Endotoxin is the lipopolysaccharide (LPS) component of the cell wall of all forms of Gram negative bacteria. The polysaccharide portion differs widely amongst the strains of various Gram negative species.  It makes up most of the “bulk” of the molecule and is the reason that the molecular weight of endotoxin ranges between 2,000 and 1,000,000 daltons.

The lipid portion of endotoxin, termed Lipid A, is identical amongst all Gram negative species.  It is also highly toxic and invokes a powerful non-specific immune response which can lead to shock and death. 

Where does it come from?

Endotoxin in the bloodstream, termed endotoxemia, comes from two sources:

• Infection - blood borne bacteria;

• Endotoxin that has crossed into the bloodstream from a compromised gut.  

Gut-derived endotoxin is a major route of exposure for patients who have undergone surgery, burns, trauma, liver failure or the critically ill.

The effects of LPS

Eukaryotic organisms and bacteria have co-existed since the origin of eukaryotic cells.  Because of this co-evolutionary exposure, humans have developed a system for recognition and removal of endotoxin.   The large amount of endotoxin in the gut makes it inevitable that the bloodstream and other tissues will be exposed to low-dose amounts of endotoxin on a regular basis. 

Endotoxin is an incredibly potent initiator of immune cascades.  Quantities as small as pg/mL injected intravenously can rapidly lead to vascular collapse, inflammation, coagulation and multiple organ failure, characteristic of severe sepsis.

Detection of Endotoxin

Endotoxin is the most important microbial mediator yet, until the EAA™, there has been no reliable method to measure it accurately in the blood stream.

The EAA™ Endotoxin Activity Assay is a rapid whole blood test. The test relies on the reaction of Lipid A with a highly specific antibody in the milieu of the patients own neutrophils. Based on the biologic principles of innate immunity, the antigen-antibody complex is phagocytized by the neutrophil, which has been primed with zymosan. The neutrophil undergoes a series of intracellular reactions resulting in the release of oxyradicals, which are captured by a reagent lumiphor.  The light units produced are counted in a chemiluminometer.  The magnitude of the priming influence amount of light over time is proportional to the concentration of antigen-antibody complexes in the patient’s blood sample.