Thermoregulation as a disease tolerance defense strategy

Physiological responses that occur during infection are most often thought of in terms of effectors of microbial destruction through the execution of resistance mechanisms, due to a direct action of the microbe, or are maladaptive consequences of host-pathogen interplay. However, an examination of the cellular and organ-level consequences of one such response, thermoregulation that leads to fever or hypothermia, reveals that these actions cannot be readily explained within the traditional paradigms of microbial killing or maladaptive consequences of host-pathogen interactions. In this review, the concept of disease tolerance is applied to thermoregulation during infection, inflammation and trauma, and we discuss the physiological consequences of thermoregulation during disease including tissue susceptibility to damage, inflammation, behavior and toxin neutralization.