Learning Outcomes:
i. Define pyrogens and explain their role in inducing fever.
ii. Describe the different types of pyrogens, including exogenous and endogenous pyrogens.
iii. Explain how exogenous pyrogens, such as microbial toxins, activate the innate immune system and lead to the release of endogenous pyrogens.
iv. Discuss the mechanisms by which endogenous pyrogens, such as prostaglandins, act on the hypothalamus to elevate body temperature.
v. Recognize the significance of fever as a protective mechanism against infections.
i. Pyrogens: The Fever-Inducing Agents
Pyrogens are substances that can induce fever, an elevation of body temperature above the normal range. Fever is a common physiological response to infection and inflammation, and it plays a crucial role in the body's defense against pathogens.
Types of Pyrogens: Exogenous and Endogenous
There are two main types of pyrogens:
Exogenous pyrogens: These pyrogens originate from outside the body, primarily from microbial sources. Microbial toxins, such as lipopolysaccharides (LPS) from Gram-negative bacteria, can activate the innate immune system, leading to the release of endogenous pyrogens.
Endogenous pyrogens: These pyrogens are produced within the body, primarily by immune cells and macrophages in response to the presence of exogenous pyrogens. Prostaglandins, a group of lipid mediators, are among the most well-known endogenous pyrogens.
ii. The Fever Response: A Multi-Step Process
The induction of fever involves a series of steps:
Activation of innate immunity: Exogenous pyrogens, such as LPS, activate immune cells and macrophages, leading to the production of endogenous pyrogens.
Action on the hypothalamus: Endogenous pyrogens, particularly prostaglandins, act on the hypothalamus, a brain region that regulates body temperature.
Resetting the thermostat: Prostaglandins increase the activity of thermogenic neurons in the hypothalamus, which elevate the body's temperature set point.
Body temperature elevation: The body's internal mechanisms, such as shivering and increased heat production, work to raise the body temperature to the new set point.
iii. Benefits of Fever: A Protective Mechanism
Fever can provide several benefits in fighting infections:
Inhibits microbial growth: Many microbes are sensitive to elevated temperatures, and fever can make it more difficult for them to replicate.
Enhances immune responses: Fever can increase the production and activity of immune cells, such as white blood cells, boosting the body's defenses.
Interferon production: Fever can induce the production of interferons, proteins that have antiviral properties.
Iron sequestration: Fever can cause the liver to release hepcidin, a protein that binds to iron, making it less available to bacteria and limiting their growth.
Fever, triggered by pyrogens, is a complex physiological response that plays a significant role in the body's defense against infections. By raising body temperature, fever creates an inhospitable environment for microbes, enhances immune responses, and promotes the production of antiviral and antibacterial substances. Understanding the mechanisms of fever induction and its benefits highlights the remarkable ability of the body to defend itself against pathogens
