Fever: pathological or physiological, injurious or beneficial?

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 TNFalpha, IL-1beta and IL-6 early during the inmate immune response, thereby obviating the risk of the potential harmful effects that could result from their dysregulated-co-expression. (C) 2002 Elsevier Science Ltd. All rights reserved.