BACKGROUND: Heat-treated cells are known to be protected from lysis by TNF, which is considered to play a central role in the pathogenesis of sepsis-induced acute lung injury. The objective of the study was to investigate the effect of heat shock response by heat-pretreatment on the acute lung injury of the rats induced by intratracheally administered TNF-alpha. METHODS: We intratracheally instilled either saline or TNF (R&D, 500ng) with and without heat pretreatment in Sprague-Dawley rats weighing 250-350 g. The heated rats were raised their rectal temperature to 41degrees C and was maintained thereafter for 13 minutes at 18 h before intratracheal administration of saline or TNF. After 5 h of intratracheal treatment, lung leak, lung myeloperoxidase activity (MPO) and heat shock proteins were measured in rats. Lung leak index was defined as counts per minute of I125 in the right lung divided by counts per minutes of I125 in 1.0 ml of blood. All data are expressed as means+/-SE. RESULTS: There is no difference in acute lung leak index (0.099+/-0.024 vs 0.123+/-0.005) among the rats given saline intratracheally with and without heat pretreatment, but MPO activity showed a decreased tendency in heat-pretreated rats (4.58+/-0.79 U/g) compared with heat-unpretreated rats (7.32+/-0.97 U/g) (P= 0.064). Rats administered TNF intratracheally with heat-pretreatment had decreased lung leak index (0.137+/-0.012) and lung MPO activity (5.51+/-1.04 U/g) compared with those of heat-unpretreated and TNF-administered rats (0.186+/-0.016, 14.34+/-1.22 U/g) (P<0.05 in each). There were no significant difference of lung leak index and MPO activity between TNF-treated rats with heat-pretreatment and saline-treated rats with and without heat-pretreatment CONCLUISON: The heat shock response attenuated neutrophil recruitment and acute lung leak induced by intratracheal instillation of TNF-in rats.