endotoxins

Endotoxins are lipopolysaccharide components of the outer membrane of most Gram-negative bacteria. They are intrinsic to the bacteria and are released during cell turnover or lysis. Endotoxins differ from exotoxins, which are proteins secreted by bacteria.

Structure and properties: Lipid A anchors the molecule in the membrane and is mainly responsible for toxic effects. The core polysaccharide and O-antigen contribute to antigenic diversity. Endotoxin molecules are relatively heat-stable and can persist after bacterial death.

Mechanism of action: Lipid A interacts with LPS-binding protein and CD14, transferring to the TLR4-MD-2 receptor complex on immune cells and triggering signaling that leads to the release of cytokines such as TNF-α, IL-1β, and IL-6. This can produce fever and a systemic inflammatory response; high levels can cause septic shock and disseminated intravascular coagulation.

Clinical and regulatory relevance: Contamination of pharmaceutical products, intravenous solutions, implants, and dialysis fluids with endotoxin can provoke fever and shock in patients. Regulatory agencies set endotoxin limits and require testing using approved assays to ensure safety of medical products and prepared drugs.

Detection and removal: The Limulus amebocyte lysate (LAL) assay is widely used for endotoxin detection; recombinant factor C assays offer an alternative. Removal and inactivation strategies include dry-heat depyrogenation, thorough cleaning, and purification steps such as ultrafiltration, ion-exchange chromatography, or affinity methods. Filtration alone does not reliably remove endotoxins.