The presence of Lipid-A in the bloodstream promotes the expression of proinflammatory cytokines and tissue factor by endothelial cells, leading to cell apoptosis. If it is released in sufficiently large quantities, Lipid-A causes the toxic effects associated with endotoxin infection in patients, including fever, diarrhea, vomiting, and possibly fatal endotoxic shock (septic shock).
Bacterial endotoxin is one of the most dangerous and common pyrogenic (fever-inducing) contaminants of parenteral pharmaceutical products, for four main reasons:
- It is ubiquitous in nature (Gram-negative bacteria can proliferate in nothing more than clean water)
- It has potent toxicity
- It is stable under extreme conditions
- It is likely to occur in the manufacturing process
Reliable and efficient testing for the presence of bacterial endotoxins is therefore essential in the pharmaceutical and biomedical industries. Any injectable or implantable products labeled as pyrogen-free or sterile must undergo endotoxin testing before release. This protects patients from harmful endotoxin poisoning, and facilitates compliance with regulatory guidelines and cGMP. The most well-established and widely used bacterial endotoxin test is the LAL assay.