Fever and hypothermia: two adaptive thermoregulatory responses to systemic inflammation

Entering both the old dispute (whether fever is adaptive or maladaptive) and its more recent modification (whether hypothermia is protective or detrimental in systemic inflammation), we suggest a new solution. We hypothesize that fever and hypothermia represent two different strategies of fighting systemic inflammation, each developed as an adaptive response to certain conditions, and each beneficial under these conditions. The antimicrobial and immunostimulating benefits of a high body temperature could be easily offset by its high energy cost. Fever, therefore, is protective only when there is no immediate threat of a substantial energy deficit. Hypothermia, on the other hand, constitutes a response aimed at energy conservation and, as such, is beneficial exactly under the conditions of a substantial energy deficit. The two thermoregulatory responses represent two complementary strategies of survival in systemic inflammation: fever ensures the active attack against the pathogen; hypothermia secures the defense of the host's vital systems. The importance of each response's contribution to the whole campaign depends on the severity of the pathogenic insult, premorbid pathology, and current conditions (stress, nutrition, ambient temperature, etc.).