Fever

Fever is one of the strongest indications of infectious disease, especially those of bacterial origin, although significant infections can occur without it. There is abundant evidence that fever is an important host defense mechanism in a number of vertebrates, including humans. Within the human body, the temperature is normally kept within a narrow range, around 37°C, by a temperature-regulation center in the hypothalamus of the brain. The hypothalamus controls temperature by regulating blood flow to the skin, and the amount of sweating and respiration. In this way, the heat produced by metabolism is conserved or lost in order to maintain a fairly constant temperature. During an infection, the regulating center continues to function but the body's thermostat is "set" at higher levels. An oral temperature above 37.8°C is regarded as fever.

A higher temperature setting occurs as a result of certain pro-inflammatory cytokines released by macrophages when their toll-like receptors detect microbial products. The cytokines are carried in the bloodstream to the hypothalamus, where they act as messages that microorganisms have invaded the body. These cytokines and other fever-inducing substances are pyrogens. Fever-inducing cytokines are called endoge-neous pyrogens, indicating that the body makes them, whereas microbial products, such as bacterial endotoxins, are called exogenous pyrogens, indicating that they are introduced from external sources. The temperature-regulating center responds to pyrogens by raising body temperature. The resulting fever inhibits the growth of many pathogens by at least two mechanisms: (1) elevating the temperature above the optimum

390 Chapter 15 The Innate Immune Response growth temperature of the pathogen, and (2) activating and speeding up a number of other body defenses.

The adverse effects of fever on pathogens correlates in part with their ideal growth temperature. Bacteria that grow best at 37°C are less likely to cause disease in people with fever. The growth rate of bacteria often declines sharply as the temperature rises above their optimum growth temperature. A slower growth rate allows more time for other defenses to destroy the invaders. ■ temperature requirements, p. 86

A moderate rise in temperature increases the rate of enzymatic reactions. It is thus not surprising that fever has been shown to enhance the inflammatory response, phagocytic killing by leukocytes, the multiplication of lymphocytes, the release of substances that attract neutrophils, and the production of interferons and antibodies. Release of leukocytes into the blood from the bone marrow is also enhanced. For all these reasons, it is wise to consult a physician before taking drugs to reduce the fever of infectious disease.

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