Background: Programmed Death 1 (PD-1) is an inhibitor protein receptor for the immune system and has been shown to be up-regulated in animal models of sepsis and after trauma and burn in humans. PD-1 may play a role in the immune dysfunction following these insults. However while prior studies have associated changes in PD-1 expression with altered immune cell function, it is not known if a correlation with clinical status exists.

Methods: Blood from daily laboratory draws were collected from both the surgical and trauma intensive care units. These samples were then processed for flow cytometry to look at various cell surface markers including CD3 and PD-1. In addition, clinical data was obtained such as presence of SIRS or sepsis, hospital mortality, and the calculated APACHE II score at the time of the blood draw. Chi square, t test, and one-way ANOVA statistics were used. The institutional review board approved this study.

Results: Thirty-two patients were included in the study resulting in 52 separate samples. Eleven samples were drawn as SIRS had resolved, 20 had SIRS, and 21 had sepsis at the time of their blood draw. Twenty-four patients had APACHE II >20, 28 were under twenty. White blood cell count and percentage of CD3+ cells were not significantly different between patients with SIRS or sepsis or when comparing patients with APACHE II above or below 20, but tended to increase with worsening illness. The percentage of CD-3+PD-1+ cells were significantly higher in patients with an APACHE II >20 (61.5% vs 41.4%, p=0.001). A trend towards an increase was seen in PD-1 expression when comparing patients that ‘resolved SIRS’ vs ‘SIRS unresolved’ and ‘sepsis’ (44.7% vs 50.3% vs 54.2%, p=0.564). As expected, those who died had significantly higher APACE II (22.11 vs 16.39, p=0.003). However, no significant difference in PD-1 expression relative to survival was seen.

Conclusion: These data indicate that the expression of PD-1 on T-cells can also be related to the extent of patient injury/physiological dysfunction. Thus, it is tempting to speculate that changes in the PD-1 expression alone or together with other markers could be a valuable diagnostic tool in delineating the development of not only immunological but also pathophysiological morbid status in the critically ill.