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There are basically two types of pyrogens:

  1. Exogenous pyrogens
  2. Endogenous pyrogens.


Exogenous pyrogens are endotoxins or lipopolysaccharide (LPS) components of Gram negative bacteria that induce fever in animal or human host when administered intravenously. Exogenous pyrogens originate outside the body and induce temperature elevations when injected into humans and animals. Examples of exogenous pyrogens include LPS, microbes, microbial components of Gram negative bacteria, fungi, viruses, Gram positive bacteria, and non-microbial components such as drugs and steroids.



Endogenous pyrogens are neither endotoxins nor LPS, but they are fever-inducing agents that arise in the body of a host when exogenous pyrogens come in contact with certain host cell molecules such as monocytes or macrophages. Endogenous pyrogens are pyrogens generated by the host body; and they have potent inflammatory and pyrogenic effects (fever-causing) in the body. Endogenous pyrogens are the primary mediators of fever in humans and animals; and they are homogenous substances produced internally in the body of a human or animal host. They are usually produced in the host in response to external stimuli (exogenous pyrogens). Typical examples of endogenous pyrogens include interleukins, tumor necrosis factor (TNF) and platelet activating factor. Cytokines and prostaglandins are typical examples of endogenous pyrogens generated by the host body.

Both endogenous and exogenous pyrogens cause a rise in the body temperature of the host. However, exogenous pyrogens are more clinically/medically significant than the endogenous pyrogens since the former (i.e., the exogenous pyrogens) enter the body of the host from the outside (especially through the administration of contaminated parenteral drugs). Pyrogens particularly LPS of Gram negative bacteria provoke an immune response in their host by producing endogenous pyrogens including prostaglandins and inflammatory cytokines such as tumor necrosis factor (TNF) and interleukins. These chemical messengers when released in the body of a human host can transmit signals to the hypothalamus of the brain, to elevate the body temperature; and this rise in body temperature (i.e., fever) could result in septic shock and possibly death if not managed effectively.

Cytokines are proteinous substances released by the cells of the lymphatic (lymph) system, and they are directly involved in controlling our body’s response to inflammation. It is however noteworthy that cytokines are usually the first messenger molecules to be released from the macrophages when our body is exposed to pyrogenic substances such as LPS. Thus, cytokines can be used as markers of infection in a human or animal host. A rise in the body’s temperature (as mediated by the activities of the cytokines) is one of the mechanisms used by cytokines to defend the body against microbial infection. And this type of defense is called innate immunity, and usually not specific in its action.

The production of cytokines by the macrophages are usually proportionate to the amount of bacterial endotoxins that invaded the host; and thus the more inflammation-inducing substances (pyrogens) there are in the host’s body, the more cytokines are produced. Hence, the reaction can be used to quantify the inflammation-inducing potential of a given sample suspected of containing pyrogens. Bacterial endotoxins and/or LPS of Gram negative bacteria stimulates the host macrophages (which are professional antigen presenting cells) to release inflammatory cytokines as aforementioned. The excessive inflammation caused in the host as a result of the release of these chemical messengers could cause multiple organ failures and death. Thus pyrogenicity is an important aspect of medical and pharmaceutical sector – owing to the significance of pyrogens in causing infection or fever in human hosts.

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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