Mouse sepsis models: don't forget ambient temperature!

Abstract

The recently published contribution by Bauer et al. [1] in this journal deciphers the heuristic value of a biological definition of sepsis as a failing stress response.Rightly, the authors proposed to expand the concept of sepsis by incorporating infectious stress within the general organismic stress response to define sepsis as an illness state characterized by allostatic overload and failing adaptive responses along with biotic (pathogen) and abiotic environmental (e.g., ambient temperature, T a ) stress factors.We want to take the opportunity to ventilate a serious shortcoming of experimental sepsis research, which compromises its translational value: the systematic disregard of T a on sepsis progression and outcome (Table 1).Textbook knowledge says that thermoregulation is a fundamental homeostatic function of all mammals.It includes afferent thermal sensing, central regulation, and an efferent response with the consequence of tightly controlled body temperature within a narrow species-specific range [2].Variations of core body temperature (T c ) outside this range trigger autonomic thermoregulatory responses, mainly via a gradually increased sympathetic activity [3].Clinical data clearly indicate that spontaneous T c lowering (hypothermia indicating energy exhaustion) is directly correlated with poor outcome of sepsis [4][5][6].Hence, in clinical settings, recommendations clearly define optimal ambient temperature ranges for appropriate care of septic patients to prevent cold stress.Therefore, T a is controlled within a narrow range of thermoneutral temperatures at which energy expenditure to maintain body temperature is lowest to save metabolic demands and prevent additional cold stress and its negative consequences on critically ill patients [7].Surprisingly, this fundamental prerequisite to warrant best possible care for patients is widely unregarded in experimental sepsis research.Mice exhibit a rather unfavorable surface area to body mass ratio as well as an unfavorable whole body thermal conductance (> one order of magnitude difference between mouse and human): therefore, already under healthy and thermoneutral conditions (similar for mouse and human at ~ 30 °C), mice have to compensate it by an enhanced basal metabolic rate.Incredibly, almost all sepsis experiments with mice are done at "room temperature"!However, these standard housing temperatures for laboratory mice, e.g., T a of 20 °C and 24 °C [8-10] induce chronic cold stress for mice.Healthy mice are capable of controlling such a challenge and maintain their core temperature through an appropriate increase of

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