Monocyte alterations, during for example, can decrease phagocytosis, inflammatory cytokine expression, and antigen presentation because of the loss of mHLA-DR expression. Lymphocyte anergy and apoptosis can ensue [3,37-39]. These changes together may increase susceptibility to infection, which in turn could provoke multiple organ failure and death.Diminished mHLA-DR expression has been proposed as a reliable biomarker of immunosuppression in ICU patients. Today, it is the most reliable marker and is used in most of the studies about ICU-acquired immunosuppression. More specifically, it has been shown to be a predictor of septic complications in several conditions, including surgical interventions, sepsis, burns, stroke, and pancreatitis [11,40-48]. Immunosuppression has long been postulated as a concomitant of trauma [37,49,50].

In regard to mHLA-DR, the pioneering work of Polk and colleagues [50] reported in 1986 revealed an association between the development of sepsis and low mHLA-DR expression. Subsequently, mHLA-DR expression was assessed as a predictor of sepsis in several series of severely injured patients [15,17,18,20,39,51-53]. A major limitation of these studies is that they were conducted over a 20-year period, during which time case management and methodologies for measurement of mHLA-DR expression have evolved, thereby complicating interpretation and comparison of the findings of these studies.In the present cohort, incidence of sepsis was 35% and the mortality rate for the entire study was 6%.

Though apparently high, these values are in concordance with those of a previous epidemiologic study by Osborn and colleagues [2], in which incidence rates of sepsis were 42% for moderate injury (defined as an ISS of between 15 and 29) and 39% for severe injury (ISS of up to 30). Another epidemiologic study in trauma patients reported a low sepsis incidence, but most of the patients presented with mild injury (ISS of less than 15: 67.7%) and no brain injury [54], the latter of which is known to be a risk factor for developing pneumonia [55-58]. In our cohort, septic patients presented more trauma brain injury than the non-septic patients did, and this is in concordance with the literature.The present study showed an overall reduction in mHLA-DR expression in trauma patients. Most importantly, in injured patients with an uneventful outcome, mHLA-DR expression returned to normal within a week.

In contrast, in patients who developed infection, mHLA-DR levels remained low or fell even lower.It would appear that the steepness of the slope of mHLA-DR recovery AV-951 is a more significant indicator than the levels attained at a given point in time. Indeed, the incidence of sepsis was significantly greater in the group with a slope of less than 1.2 (days 3 and 4/days 1 and 2).