Fever is present when the core temperature is about 100˚F (37.8˚C) (99˚F/ 37.2˚C in AM, 100˚F/37.8˚C in PM). The hypothalamus maintains the internal or core temperature at a set point of about 97-99.8˚F (36.1-37.7˚C).
Fever resets the set point to a higher degree. Thus, even though the body is hot, it feels cold because the set-point has been raised. Mechanisms to conserve heat, such as vasoconstriction and shivering, are activated.
Bacteria, viruses, phagocytized breakdown products and toxins stimulate monocytes and macrophages to release endogenous pyrogenic cytokines. Antigen-antibody complexes, metabolites and dead tissue sometimes evoke the same response. The main pyrogenic cytokines are interleukin-1, interleukin-2 and tumor necrosis factor. These cytokines induce formation of a prostaglandin (PGE-2) in the temperature center (thermoregulatory
center) of the hypothalamus. Prostaglandin resets the normal set point (~98.6˚F) to a higher degree.
The majority of fevers are caused by infection, but some are the result of malignancy, stroke and an assortment of allergic and autoimmune disorders. In the typical case, microorganisms are killed, antibody production, an important facet of the immune response, is enhanced and white blood cells show increased phagocytic activity.
Since fever activates mechanisms that increase metabolism and heat production, there is an increase in heart rate, respiratory rate and blood pressure (primarily systolic). The heart rate is elevated by about 9-10 beats for each degree Fahrenheit increase in temperature. The mental status is sometimes affected but brain damage does not occur unless symptoms of heat stroke appear (sustained temperature over 106˚F/41.1˚C), or meningo-encephalitis is also present.
Antifever drugs (antipyretics) such as aspirin, acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs such as ibuprofen (Advil, Motrin) and naproxen (Naprosyn, Anaprox) act on the hypothalamus by blocking prostaglandin synthesis. Steroids block both prostaglandins and endogenous pyrogen, but are weak antipyretics.
Antipyretics are routinely administered for fever, although the increase in temperature is a primary defense against infection. The body raises the setpoint to kill microorganisms which survive poorly in a hot environment. As the temperature increases, phagocytic activity and antibody production increase.
When the temperature falls after the administration of antipyretics, phagocytic activity and antibody production decrease. Recent studies have shown that the administration of antipyretic agents prolong the course of infection. It is reasonable to use antipyretics to treat uncomfortable patients and those with temperatures approaching hyperthermia (105˚F, 40.6˚C).