Response of mice to continuous 5-day passive hyperthermia resembles human heat acclimation

Abstract

Chronic repeated exposure to hyperthermia in humans results in heat acclimation (HA), an adaptive process that is attained in humans by repeated exposure to hyperthermia and is characterized by improved heat elimination and increased exercise capacity, and acquired thermal tolerance (ATT), a cellular response characterized by increased baseline heat shock protein (HSP) expression and blunting of the acute increase in HSP expression stimulated by re-exposure to thermal stress. Epidemiologic studies in military personnel operating in hot environments and elite athletes suggest that repeated exposure to hyperthermia may also exert long-term health effects. Animal models demonstrate that coincident exposure to mild hyperthermia or prior exposure to severe hyperthermia can profoundly affect the course of experimental infection and injury, but these models do not represent HA. In this study, we demonstrate that CD-1 mice continuously exposed to mild hyperthermia (ambient temperature ~37°C causing ~2°C increase in core temperature) for 5 days and then exposed to a thermal stress (42°C ambient temperature for 40 min) exhibited some of the salient features of human HA, including (1) slower warming during thermal stress and more rapid cooling during recovery and (2) increased activity during thermal stress, as well as some of the features of ATT, including (1) increased baseline expression of HSP72 and HSP90 in lung, heart, spleen, liver, and brain; and (2) blunted incremental increase in HSP72 expression following acute thermal stress. This study suggests that continuous 5-day exposure of CD-1 mice to mild hyperthermia induces a state that resembles the physiologic and cellular responses of human HA. This model may be useful for analyzing the molecular mechanisms of HA and its consequences on host responsiveness to subsequent stresses.

A comparative study on the expression profile of MCTs and HSPs in Ghungroo and Large White Yorkshire breeds of pigs during different seasons

“…Our present study found that the mRNA expression of HSP90 in both the breeds during the summer season was significantly higher (P<0.05) than the corresponding values in thigh muscle during the winter season. Our findings are in accordance with previous studies in which heat stress-induced HSP90 expression was observed in the goat PBMCs (Dangi et al 2012), in human blood lymphocytes (Schimidt and Abdulla 1988), and in lung, heart, spleen, liver, and brain of human (Sareh et al 2011). The increased expression during the summer season could provoke its transcription to protect cells from the damaging effects of heat stress such as the denaturation of proteins, help in protein refolding, and prevent aggregation of denatured proteins (Dangi et al 2012).…”

Toll-like Receptor Agonists and Febrile Range Hyperthermia Synergize to Induce Heat Shock Protein 70 Expression and Extracellular Release

“…Intratracheal LPS Challenge Enhanced Hsp70 Expression in Lung of Hyperthermic Mice-As we have previously shown (33,34), mice housed at 36 -37°C ambient temperature increased their core temperature by ϳ2.5°C to 39 -40°C and maintained the same activity level and circadian temperature pattern as in normothermic mice (Fig. 7A).…”

“…To avoid the influence of diurnal cycling, all of the experiments were started at approximately the same time each day (between 8:00 and 10:00 a.m.). One sentinel mouse/experimental group was implanted with an intraperitoneal telemetric thermistor (Data Safety International, St. Paul, MN; ETA-F10) as we have previously described (33,34) and allowed to recover for 7 days prior to further experimentation. Exposure to hyperthermia and LPS challenge and core temperature monitoring was performed as described in our previous studies (33,34).…”

“…Normothermic controls were handled and housed in the same way except at standard room temperature (24 -25°C). In conscious unrestrained mice, such exposures maintain core temperatures of 39.5-40 and 36.5-37°C, respectively (33,34). For LPS instillation, the mice were briefly anesthetized with isoflurane, and 50 g of LPS in 50 l of PBS was administered into the posterior pharynx with the tongue retracted until aspiration was witnessed.…”

Febrile-Range Hyperthermia Modifies Endothelial and Neutrophilic Functions to Promote Extravasation

“…Some mice received 200 mg U0126, 1 mg SB203580, or 2% DMSO (sham) intraperitoneally, 30 minutes before FRH. Core temperature was monitored using ETA-F10 intraperitoneal thermistors (Data Sciences International, St. Paul, MN), placed 10 days earlier (19).…”