Journal of Thermal Biology 28 (2003) 1–13
Fever: pathological or physiological, injurious or beneficial?
Clark M. Blatteis*
Department of Physiology, College of Medicine, The University of Tennessee Health Science Center, 894 Union Avenue,
Memphis, TN 38163 USA
Received 17 February 2002; accepted 19 June 2002
Fever, the body’s most manifest sign of infectious illness, is only one of a concatenation of complex, nonspecific host
defense responses to infectious pathogens termed the acute-phase response. It develops in most endotherms via the
activation of a combination of various autonomic and behavioral mechanisms. It also occurs in many ectotherms, most
usually as the result of behavioral processes alone. Although fever may shorten disease duration and improve survival,
antipyretic medications are nonetheless routinely prescribed, with apparently negligible adverse effects on the course
and outcome of the disease. The popularity of antipyretics is probably due mostly to their moderating effects of the
discomfort level and consequent alleviation of the anxiety of afflicted patients and/or their caregivers. But is treatment
of fever really indicated? Would letting fever run its natural course be better? Recent data suggest that, while heat/fever
may kill some pathogenic microbes, this would not seem to be its principal role. Rather, heat/fever would appear to
serve an important adjuvant function by enhancing the effectiveness of certain selective, stimulus-activated adaptive
immune responses and thereby helping to compartamentalize the acute-phase response to the infected site. But arguably
even more important may be its temporal modulation of the stimulus-induced generation of TNFa, IL-1b and IL-6
early during the innate immune response, thereby obviating the risk of the potential harmful effects that could result
from their dysregulated co-expression.
r 2002 Elsevier Science Ltd. All rights reserved.
‘‘Humanity has but three great enemies: fever, famine
and war. Of these, by far the greate