ABSTRACT
Pyrogens are products of metabolism of microorganisms. The most potent pyrogenic substances (endotoxins) are constituents (lipopolysaccharides, LPS) of the cell wall of gram-negative bacteria (e.g., Pseudomonas sp, Salmonella sp, Escherichia coli). Gram-positive bacteria and fungi also produce pyrogens but of lower potency and of different chemical nature. Gram-positive bacteria produce peptidoglycans while fungi product -glucans, both of which can cause nonendotoxin pyrogenic responses. Endotoxins are LPS that typically exist in high-molecular-weight aggregate forms. However, the monomer unit of LPS is less than 10,000 Da, enabling endotoxin easily to pass through sterilizing 0.2-m filters. Studies have shown that the lipid portion of the molecule is responsible for the biological activity. Since endotoxins are the most potent pyrogens and gram-negative bacteria are ubiquitous in the environment, especially water, this discussion focuses on endotoxins and the risk of their presence as contaminants in sterile products.
