Sunday 13 December 2009, 23:22

Fever: what is it?

Pathogenesis of fever

Fever: what is it?

The term “fever” is used to mean an elevation in core body temperature above the accepted normal value of 37 °C, due to the so-called pyrogenic substances and generally associated with infection or other inflammatory processes.


In other words, fever is a non-specific physiological response to infection and/or inflammation. It is therefore a symptom of a variety of different diseases and is not a disease in itself. Mild-moderate fever is rarely fatal and may be beneficial to the body: it increases leukocytes function, inhibits viral replication and decreases the uptake of iron by bacteria (iron is essential for bacterial growth and replication). However, when fever exceeds 40-41 °C, there exists a significant risk of permanent organ damage and disseminated intravascular coagulation (DIC).


Which is the pathogenetic mechanism of fever? In normal physiological conditions, core body temperature is maintained within a narrow range (normothermia) through a delicate balance between heat dissipation on the one hand and heat production and conservation on the other hand. The hypothalamic thermoregulatory center of the brain functions as a thermostat, set at a certain temperature called “set-point” (between 36 °C and 37 °C in humans). Whenever core temperature rises above or falls below the set-point, the thermoregulatory center stimulates the body to dissipate heat if the body is too warm or to increase heat production and conservation if the body is too cold.


Fever results from a resetting of the set-point to a higher value. It is initiated by a variety of substances called “exogenous pyrogens”, including infectious agents and/or their products, soluble antigen-antibody complexes, pharmacologic agents, products derived from tissue inflammation or necrosis.


In response to the stimulus by an exogenous pyrogen, certain immune cells (macrophages) release specific proteins called “endogenous pyrogens”, of which the most important is interleukin-1 (IL-1). Endogenous pyrogens are then transported via the bloodstream to the hypothalamus, where they cause the release of prostaglandin E2 (PGE2). It is PGE2 that is responsible for the elevation of the set-point. Once set-point has been raised, fever response occurs: the core body temperature raises through increased heat production (e.g. shivering) and conservation (e.g. vasoconstriction, postural changes, seeking warm environment). The mechanism described above explains why non-steroidal anti-inflammatory drugs or NSAIDs (inhibitors of PGE2 synthesis, such as aspirin) are effective in reducing fever.


It is important to stress that not all the elevations in core body temperature (hyperthermic states) are associated with an elevation of the hypothalamic set-point. In hyperthermic states other than fever, such as heat stroke, exercise hyperthermia, seizures disorders and hypermetabolic disorders, hyperthermia is the result of physiologic or pathologic conditions where heat gain exceeds heat loss. In these cases PGE2 is not involved and NSAIDs are of limited or null effectiveness. In non-pyrogenic hyperthermia body temperature has to be lowered by physical means (for example cool water baths or rinses).


By Chiara De Carli

Category: Health

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