Heat stress protects from cardiovascular collapse but does not prevent pulmonary inflammation in rat sepsis

Introduction: Heat stress prior to sepsis has been shown to attenuate cardiopulmonary injury and improve survival. The mechanism of protection is unknown but may be related to suppression of the inflammatory response. The objective of this study was to determine if heat stress protected the lung in sepsis by decreasing leukocyte infiltration and modulating cytokine production. Methods: Rats were assigned to one of 4 groups. Group 1 rats (n=10) were heated to 41-42°C for 10-15 min. had cecal ligation and perforation (CLP) 20 hrs later and then were sacrificed 20 hrs after CLP. The lungs were lavaged and the alveolar macrophages (AM) were counted and incubated overnight. Group 2 rats (n=10) were treated as group 1 rats except for heating. Group 3 (n=6) and group 4 (n=6) rats had sham CLP. Group 3 was heated and group 4 was not. Blood was obtained for lactate and plasma, lavage, and AM supernatant were collected for TNFα, IL-1β, and macrophage inflammatory protein (MIP)-2. Myeloperoxidase (MPO) activity was determined in the lung tissue. One way ANOVA was used to compare groups and Student-Newman-Keuls post-hoc test was used when necessary. Results: Lactate production was increased in rats which had CLP without heating (group 2) when compared to groups 1, 3, 4 (4.1±.8 vs. 2.4±.4, 2.0±.5, 1.0±.2 mmol/L respectively, p<0.05). The lungs from the CLP rats had increased MPO compared to the sham rats , however, heat pretreatment did not attenuate leukocyte infiltration (fig). TNF-α, IL-1β or MIP-2 were not detected in plasma. Lavage fluid of CLP rats contained TNF-α and MIP-2, however heat did not influence their concentrations. In CLP rats, AM supernatant contained more MIP-2 in the heated rats than unheated rats, (735±77 vs. 448±94 pg/ml, p<0.02). Conclusions: Heat stress protects by preserving organ perfusion in sepsis. Previously demonstrated pulmonary protection by heat is not due to decreased leukocyte infiltration. The mechanism of salutary effects of heat-induced MIP-2 production by AM needs to be explored.