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A pyrogen is simply defined as a fever-causing (inducing) agent that includes toxins of microorganisms. The phrase “pyrogens” is derived from the Greek word “Pyros” to mean “Fire”. Pyrogens are the lipopolysaccharide (LPS) component or endotoxins of bacteria especially Gram negative organisms. They also include the cell wall components of both Gram negative and Gram positive bacteria capable of inducing fever in human or animal hosts. Endotoxins are part of the outer membrane of the cell wall of Gram-negative bacteria; and they are invariably associated with Gram-negative bacteria whether the organisms are pathogenic or not. LPS also known as bacterial endotoxin and found in the cell membrane of Gram negative bacteria is the best studied pyrogen of bacteria. LPS are the main components of the cell wall or cell membrane of Gram negative bacteria; and they are generally pyrogenic in nature (Figure 1). They are very heat-stable in nature and therefore are not easily destroyed under normal sterilization conditions. Bacterial endotoxins or LPS are ubiquitous in nature and can be found in the air, water, in the laboratory and even at work environments.

Figure 1. Illustration of Gram negative cell membrane. Photo courtesy:


Human activities and/or occupation that leads to the production and release of infectious particles containing microbes such as dust can make pyrogens to become airborne – through which possible human contamination or infection can occur. Good manufacturing practice (GMP) requirements for the production of sterile products requires that sterile pharmaceutical or medical products be free from particulate matter, microbiological contamination and pyrogens in particular. Pyrogens could be parts of microbial cells including parts of bacteria, fungi and viruses; and these parts of microbial cells are of immense medical importance because of the untoward reactions such as fever and shock that they can cause in the human body.

The pyrogenic principles of bacteria especially Gram negative bacteria are usually attributable to some heat-stable substances secreted by these organisms; and which if found in parenteral drugs could induce fever (a rise in the body temperature of the host taking the medication). This phenomenon necessitates the need to continuously test and detect the presence of pyrogens in intravenous medications and other parenterals so that the batch of the products containing fever-inducing agents could be stopped from reaching the general public.

Fever as we know it is one of the major symptoms or clinical signs of an infectious disease including those caused by viruses, fungi, protozoa and bacteria. The notable pyrogenic substances are usually the endotoxins of Gram negative bacteria especially the LPS component of Gram negative bacteria cell wall. Other pyrogenic substances include exotoxins from Gram positive bacteria such as Streptococcus species and enterotoxins from Staphylococcus aureus.The lipoteichoic acid (LTA) components of Gram positive bacteria are also pyrogenic in nature (i.e. they are fever-inducing agents).

Further reading

Bushell M.E (1998). Application   of   the   principles   of   industrial   microbiology   to   biotechnology (ed. Wiseman, A.) Chapman and Hall, New York.

Byong H. Lee (2015). Fundamentals of Food Biotechnology. Second edition. Wiley-Blackwell, New Jersey, United States.

Frazier W.C, Westhoff D.C and Vanitha N.M (2014). Food Microbiology. Fifth edition. McGraw-Hill Education (India) Private Limited, New Delhi, India.

Jay J.M (2005). Modern Food Microbiology. Fourth edition. Chapman and Hall Inc, New York, USA.

Bushell M.E (1998). Application   of   the   principles   of   industrial   microbiology   to   biotechnology (ed. Wiseman, A.) Chapman and Hall, New York.

Farida A.A (2012). Dairy Microbiology. First edition. Random Publications. New Delhi, India.

Nduka Okafor (2007). Modern industrial microbiology and biotechnology. First edition. Science Publishers, New Hampshire, USA.

Roberts D and Greenwood M (2003). Practical Food Microbiology. Third edition. Blackwell publishing Inc, USA.

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