Heat shock response decreases endotoxin‐induced acute lung injury in rats

Transient whole‐body hyperthermia was reported to reduce lung damage in a rat with intra‐abdominal sepsis produced by caecal perforation.

Methodology: In order to determine the effect of heat shock response on acute lung injury induced by endotoxin, which plays a central role in the pathogenesis of sepsis, we instilled either saline or lipopolysaccharide (LPS) intravenously with and without heat pretreatment in rats. The heated rats had their rectal temperature raised to more than 40°C for 13 min 18 h before intravenous administration of saline or LPS.

Results: We found that the lung leak was significantly increased among the rats given LPS intravenously with (median, 0.17; range, 0.15–0.22; n = 10) and without heat pretreatment (0.23; 0.17–0.30; n = 10) compared with those of saline‐treated rats (0.13; 0.10–0.14; n = 10) (P < 0.05 in each). However, rats given LPS after heat pretreatment had significantly decreased lung leak index compared with those of LPS‐treated rats without heat pretreatment (P < 0.05). Rats administered LPS intravenously showed increased myeloperoxidase activity without heat pretreatment (19.01; 9.34–28.00 U/g; n = 10) compared with that of saline‐treated rats (7.09; 4.49–10.56 U/g; n = 5) (P < 0.05) ( Fig. 2). Myeloperoxidase activity of the rats treated with LPS with heat pretreatment (5.57; 2.87–8.96 U/g; n = 10) was significantly decreased to the level of normal control compared with that of LPS‐treated rats without heat pretreatment (P < 0.05). The levels of heat shock proteins (HSP72) in lung tissue, which were examined by western blot analysis, were increased over baseline levels at 23 h after hyperthermic stress.

Heat pretreatment decreased lung myeloperoxidase (MPO) activity in rats administered lipopolysaccharide (LPS; 3 mg/kg) intravenously. The number of determinations is shown in parentheses. *P < 0.001 compared with saline‐treated rats. **P > 0.05 compared with saline‐treated rats. Boxplot: Box = 25–75 percentile; bold line, median value; whiskers indicate the minimum and maximum values.