Inducibility of the 70 kD heat shock protein in peripheral blood monocytes is decreased in human acute respiratory distress syndrome and recovers over time

The heat shock/stress proteins (HSP), and, in particular, the inducible, cytosolic Hsp70, represent an extremely conserved response to many different cellular injuries, including reactive oxygen species (ROS). Hsp70 has been shown to confer to cells and tissues protection against the deleterious effects of ROS or cytokines, both in vitro and in animal models of acute respiratory distress syndrome (ARDS). We hypothesized that Hsp70 expression levels in peripheral blood monocytes (PBM) of patients with ARDS, would correlate with disease severity. We prospectively included 13 patients with previous ARDS (50 +/- 17 yr; range, 20 to 76 yr), nine ventilated patients with non-ARDS/ALI disease (45 +/- 20 yr; range, 19 to 76 yr), and 14 healthy volunteers (45 +/- 20 yr; range, 22 to 77 yr). PBM activation state was evaluated according to their membrane expression of CD16, and oxidative status according to plasma lipid peroxidation products. Both baseline expression and Hsp70 inducibility (after in vitro heat shock) were examined in PBM, using flow cytometric analysis. We found that basal expression of Hsp70 in PBM was similar for patients and control subjects, whereas Hsp70 inducibility - a reflection of the ability to mount a stress response - was significantly reduced in the patients with ARDS (p = 0.02). Among all correlation analyses we considered between Hsp70 inducibility on the one hand, clinical and laboratory biomakers for disease severity and outcome in the patients with ARDS on the other, only the duration of ventilatory support was significant (p < 0.003). As an approach to distinguish between disease and ventilation, we also analyzed a group of, ventilated patients without ARDS. Our results indicate that in patients with ARDS, Hsp70 inducibility in PBM is decreased, but it recovers over time with duration of ventilatory support.