For example, the use of antipyretic drugs to diminish fever correlates with a 5% increase in mortality in human populations infected with influenza virus and negatively affects patient outcomes in the intensive care unit. 2 There is mounting evidence that the increase of 1 to 4☌ in core body temperature that occurs during fever is associated with improved survival and resolution of many infections. 1 The induction of fever in endothermic (warm-blooded) animals occurs at a high metabolic cost such that a 1☌ rise in body temperature requires a 10–12.5% increase in metabolic rate. Febrile temperatures are so closely linked to the inflammatory response that heat (calor) is one of the four cardinal signs of inflammation, along with pain (dolor), redness (rubor), and swelling (tumour), as described by Celsus in ~30 BC. The fever response is a hallmark of infection and inflammatory disease and has been shaped through hundreds of millions of years of natural selection.
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