Thermal Restriction as an Antimicrobial Function of Fever.

Abstract

Calor (heat), rubor (redness), tumor (swelling), and dolor (pain) are the cardinal signs of inflammation. To these can be added loss of function by inflamed tissues. Of the cardinal signs, calor, or fever, is a common response to infection. Fever is an evolutionarily conserved host response to microbial infection that has been described in organisms from such diverse phyla as Chordata, Arthropoda, and Annelida [1]. Fever has been defined as “a state of elevated core temperature, which is often, but not necessarily, part of the defensive responses of multicellular organisms (host) to invasion of live (microorganisms) or inanimate matter recognized as pathogenic or alien to the host” [2]. It is noteworthy that this definition views fever as an increased temperature, and in this essay we will focus on the effects of temperature on host defense. For endothermic and homoeothermic organisms like mammals, fever reflects an increase in metabolism such that maintaining a fever temperature 2°C above the afebrile state can increase metabolism by 20% [3]. For ectothermic organisms, fever can result from increased metabolic activity and/or be induced by increased physical activity or exposure to warm sources like the sun. In insects and ectothermic invertebrates, there is a large body of evidence showing that fever is beneficial to the host during microbial infection [3]. However, in mammals, some have questioned whether this increase in metabolism over an already high baseline is beneficial and suggested that the risks and discomfort associated with increased temperature outweigh any benefits [4], a view that also considers fever as an unpleasant side effect of the response to infection. An unequivocal demonstration of the benefits of fever in mammals has proved elusive, with some studies supporting a beneficial role for fever, while others note detrimental effects [1,5,6]. While there is no question that life-threatening elevations in temperature require antipyretic treatment, there is much less consensus on how to approach common fevers. Perhaps the best evidence for a dismissive approach to the value of fever in humans is the fact that physicians, nurses, and parents reflexively respond to fever by administering antipyretics [5,7,8].