Matt Harmon

57 Chapter three Figure 3 . Whole-blood leukocyte responsiveness to LPS stratified according to the presence of hypothermia. 0 500 1000 1500 2000 2500 3000 TNF− α (pg/ml) 0 50 100 150 200 250 300 IL−1 β (pg/ml) No hypothermia Healthy subjects Hypothermia TNF- α IL-1 β ** * ** Responsiveness of whole-blood leukocytes to lipopolysaccharide (LPS) was reduced compared to healthy subjects (n = 18), but not different between hypothermic (n = 5) and nonhypothermic (n = 10) patients with sepsis. Box and whisker diagrams depict the median and lower quartile, upper quartile, and respective 1.5 IQR as whiskers. * P < 0.05, ** P <0.01. Hypothermia is associated with increased plasma levels of the endothelial cell activation marker fractalkine All markers of endothelial dysfunction were higher in patients with sepsis compared to healthy controls, except angiopoetin-1, which were lower (Figure 4). Angiopoietin-2 and the ratio of angiopoietin-2/angiopoietin-1 were higher in hypothermic patients on day 2 compared to nonhypothermic patients with sepsis. This difference was not present at the other time points. Strikingly, levels of fractalkine, an endothelial cell derived chemokine, were substantially higher in hypothermic versus nonhypothermic patients on the day of admission (Figure 4). These differences persisted on days 2 and 4 after admission. To determine whether the higher levels of fractalkine in the hypothermic group were due to differences in disease severity, every hypothermic patient was matched to a nonhypothermic patient with a comparable APACHE IV score. Patient characteristics of the matched cohort are shown in Supplemental Table 6. In the subsequent analysis, fractalkine remained significantly higher in patients with hypothermia (median levels admission 28.5 pg/ml vs 20.8 pg/ml, P =0.005,