Monocyte Deactivation Correlates With Injury Severity Score, But Not With Heme Oxygenase-1 Levels in Trauma Patients

Abstract

Traumatic injury induces a local and systemic release of pro-inflammatory cytokines, acute phase proteins, hormones and other inflammatory mediators. The excessive release of these mediators plays an important role in the pathogenesis of shock. In parallel to this pro-inflammatory response, there is a regulatory response characterized by the release of anti-inflammatory mediators, which is thought to represent the host’s attempt to restore immunological equilibrium. Studies in septic patients have suggested the compensatory anti-inflammatory response may result in an “immunodeficient state” that leaves the host susceptible to further infectious insults. A key feature of the anti-inflammatory state in septic patients is a change in the responsiveness of monocytes that has been termed “monocyte deactivation.” This is supported by data that link monocyte deactivation to increased mortality in septic patients. Monocytes with reduced HLA-DR expression have been described in trauma patients. We collected blood from 25 severely injured patients and evaluated peripheral blood mononuclear cells (PBMC) for HLA-DR expression and TNF-alpha response to LPS stimulation as markers of monocyte deactivation. Levels of intracellular HO-1 were determined in each patient, as HO-1 has been implicated in monocyte deactivation in patients with severe SIRS. HLA-DR expression correlated inversely with Injury Severity Scores and TNF-alpha response to LPS stimulation, but failed to correlate with HO-1 levels in these patients. HLA-DR expression was decreased in normal monocytes stimulated with patient plasma, but this treatment had no effect on HO-1 levels. These results suggest monocyte deactivation in trauma patients is unlikely to be mediated by HO-1.

HLA-DR expression on monocytes is decreased in polytraumatized patients

“…Decreased expression of HLA-DR on monocytes is a hallmark of altered immune status in patients with SIRS. West et al could show that HLA-DR expression on monocytes correlates with injury severity [ 25 ]. They could also show decreased monocytic HLA-DR levels 48 h after trauma as others have shown before [ 25 , 26 ].…”

Nosocomial infections after severe trauma are associated with lower apolipoproteins B and AII

“…All samples and information were obtained in accordance with the guidelines and protocols approved by Human Research Protections Office at the UNM Health Science Center. A subset of this study’s patient population was previously characterized [11]. This study is a nested case-control study that is a pre-planned secondary analysis of a convenience sample of prospectively identified patients who had suffered severe trauma.…”

“…Severe trauma causes profound disruptions in homeostasis measureable by alterations in soluble mediators of inflammation [6,10], defects in phagocyte function [11–14], and abnormal coagulation [15] that are thought to contribute to the immunosuppression that follows severe trauma [16]. Because serum lipoprotein concentrations, including high density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL), are also altered by the acute inflammatory response [17], we postulated that circulating levels of lipoproteins might be altered following severe trauma.…”

Transforming Growth Factor-β, Macrophage Colony-Stimulating Factor and C-Reactive Protein Levels Correlate with CD14highCD16+ Monocyte Induction and Activation in Trauma Patients

“…No patients were included that were admitted to the ICU for merely observation status. Results from a portion of this patient cohort were previously published [20]. These patients were a prospectively collected convenience sample of sequential patients who had suffered severe trauma and were able to provide written informed consent or had a legally authorized representative who was able to provide written informed consent.…”