Pyrogens are foreign material or substances that, when they gain systemic access to the body in a sufficient concentration, lead to increased body temperature. Most pyrogens are derived by microorganisms. The range of possible pyrogenic effects include a febrile response (elevated temperature), inflammation, shock, multiorgan failure, and even death.
There are different types of pyrogens, and they can be divided into endotoxins and non-endotoxic pyrogens.
Endotoxins, which are also known as lipopolysaccharides (LPS) and lipoglycans, are the most widely known pyrogens and are a component of the outer membrane of gram-negative bacteria, including E. coli, Salmonella, and Pseudomonas.
Non-endotoxic pyrogens are derived from other microorganisms, including gram-positive bacteria, viruses, yeasts, and fungi, or from chemical substances. Non-endotoxic pyrogens may include lipoproteins, peptidoglycans, and lipoteichoic acids.
Chemically, endotoxins include two major components, namely, lipid A and the polysaccharide O-region. Lipid A plays a key role for endotoxin toxicity, whereas the polysaccharide components are important for endotoxin immunogenicity.
Endotoxins have been implicated in the recognition of gram-negative bacteria by the host organism and in the induction of an inflammatory and immune response (e.g. fever reaction). The mechanisms implicated in these effects begin with the release of endotoxins from gram-negative bacteria primarily during their bacteriolysis. The released endotoxins are then transported to the CD14 receptor expressed on the surface of immune cells by the lipid-binding protein (LBP). The subsequent binding of endotoxins to the CD14/TLR4/MD2 complex initiates a downstream inflammatory and immune response, including activation of the transcription factor NF-κβ, the complement, and the coagulation cascade.
Pyrogens, including endotoxins, are widely spread in the environment, including in the air, water, soil, and even the surfaces of the human body. However, systemic access of exogenous pyrogens, including endotoxins, into the cardiovascular or lymphatic system or the cerebrospinal fluid can have severe consequences. As it is extremely challenging to eliminate pyrogen after production, including endotoxin contamination, all efforts should be made to maintain reagents used in laboratories pyrogen-free.
There are strict requirements for pyrogen testing for all parenteral drugs or solutions coming into contact with the patient’s bloodstream, such as dialysate solutions. Moreover, medical devices, which come into direct (such as implantable medical devices or needles) or indirect (during the manufacturing process of drugs and solutions) contact with the bloodstream should also be subjected to testing for pyrogens.
Historically, the rabbit pyrogen test was one of the initial methods for detection of pyrogens. However, it has since been largely replaced by in vitro pyrogen tests. From the point of view of pharmaceutical laboratories, endotoxins are considered the most important pyrogens. Therefore, the Limulus amebocyte lysate (LAL) assay, which detects bacterial endotoxins in analyzed samples, is the most widely used test for endotoxin (pyrogen) testing. Our SLP-kit is complementing our pyrogen-detection portfolio by being able to detect two specific non-endotoxin pyrogens (1->3- β- D-glucan and peptidoglycan) from gram-positive bacteria and fungi.
We have developed a set of reliable and accurate pyrogen tests, which have found applications both in the fields of research and diagnostics. Moreover, our Diagnostics department can provide detailed guidance regarding the diagnostic use of our pyrogen tests.