What are the mechanisms leading to pyrexia (fever)?

From the Guidelines

Fever is primarily caused by the body's immune response to infection or inflammation, triggered by the release of pyrogens such as cytokines, which reset the body's temperature setpoint higher, leading to increased heat production and reduced heat loss. When pathogens like bacteria or viruses invade the body, immune cells release these chemicals, particularly cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor-alpha 1. These pyrogens travel through the bloodstream to the hypothalamus, the brain's temperature control center, where they trigger the production of prostaglandin E2. This chemical resets the body's temperature setpoint higher, causing the body to increase heat production through shivering and reduce heat loss through vasoconstriction. Non-infectious causes like autoimmune disorders, certain medications, and some cancers can also trigger this pyrogen-mediated process 1. The elevated temperature serves a protective function by enhancing immune function, slowing pathogen reproduction, and creating an unfavorable environment for many microorganisms. Fever-reducing medications like acetaminophen and ibuprofen work by inhibiting prostaglandin synthesis, effectively lowering the reset temperature setpoint in the hypothalamus.

Some key points to consider in the mechanisms leading to fever include:

• The role of cytokines and other pyrogens in triggering the immune response and resetting the body's temperature setpoint 1
• The importance of the hypothalamus in regulating body temperature and responding to pyrogens 1
• The potential for non-infectious causes, such as autoimmune disorders and certain medications, to trigger fever 1
• The protective function of fever in enhancing immune function and slowing pathogen reproduction 1

It's worth noting that the evidence from the provided studies 1 supports the idea that fever is a complex process involving multiple mechanisms and pathways, and that a comprehensive understanding of these mechanisms is essential for effective diagnosis and treatment of fever-related illnesses.

From the Research

Mechanisms of Fever

The mechanisms that lead to fever are complex and involve various physiological processes.

• The febrile response is a cytokine-mediated rise in body temperature, generation of acute-phase reactants, and activation of numerous endocrinologic and immunologic systems 2.
• Fever represents a complex physiological, adaptive host response that is beneficial for host defense and survival but can be maladaptive and harmful if left unabated 3.
• The production of fever is a result of the body's natural defense mechanisms, and its suppression may interfere with these mechanisms, potentially worsening patient outcomes 4.

Pathophysiology of Fever

The pathophysiology of fever involves multiple systems and processes, including:

• A cytokine-mediated rise in body temperature 2.
• Generation of acute-phase reactants 2.
• Activation of numerous endocrinologic and immunologic systems 2.
• Systemic inflammation, multiorgan dysfunction, and poor neurological recovery 3.

Etiology of Fever

Fever can be caused by a wide range of conditions, including:

• Infections 5, 6.
• Noninfectious causes, such as inflammation or immune responses 6, 3.
• Various disease conditions, affecting up to 70% of patients in the intensive care unit (ICU) 3.