How murine models of human disease and immunity are influenced by housing temperature and mild thermal stress

At the direction of The Guide and Use of Laboratory Animals, rodents in laboratory facilities are housed at ambient temperatures between 20°C and 26°C, which fall below their thermoneutral zone (TNZ). TNZ is identified as a range of ambient temperatures that allow an organism to regulate body temperature without employing additional thermoregulatory processes (e.g. metabolic heat production driven by norepinephrine), thus leading to mild, chronic cold stress. For mice, this chronic cold stress leads to increased serum levels of the catecholamine norepinephrine, which has direct effects on various immune cells and several aspects of immunity and inflammation. Here, we review several studies that have revealed that ambient temperature significantly impacts outcomes in various murine models of human diseases, particularly those in which the immune system plays a major role in its pathogenesis. The impact of ambient temperature on experimental outcomes raises questions regarding the clinical relevance of some murine models of human disease, since studies examining rodents housed within thermoneutral ambient temperatures revealed that rodent disease pathology more closely resembled that of humans. Unlike laboratory rodents, humans can modify their surroundings accordingly – by adjusting their clothing, the thermostat, or their physical activity – to live within the appropriate TNZ, offering a possible explanation for why many studies using murine models of human disease conducted at thermoneutrality better represent patient outcomes. Thus, it is strongly recommended that ambient housing temperature in such studies be consistently and accurately reported and recognized as an important experimental variable.