Traumatic Injury, Early Gene Expression, and Gram-Negative Bacteremia*

Abstract

Rationale Bacteremic trauma victims have a higher risk of death than their non-bacteremic counterparts. The role that altered immunity plays in the development of bacteremia is unknown. Objective Using an existing dataset, we sought to determine if differences in early post-injury immune-related gene expression are associated with subsequent gram-negative bacteremia (GNB). Design Retrospective cohort study, a secondary analysis of the Glue Grant database. Subjects Severely injured blunt trauma patients. Setting Seven level one trauma centers across the United States. Measurements Total leukocyte gene expression was compared between the subjects that developed GNB and those that did not. Main Results We observed that GNB was an independent risk factor for death (OR, 1.86; P=0.015). We then compared gene expression at 12 and 96 hours after injury in ten subjects who subsequently developed GNB matched to 26 that did not. At 12 hours, expression of 64 probes differed ≥1.5-fold; none represented genes related to innate or adaptive immunity. By 96 hrs, 102 probes were differentially expressed with 20 representing 15 innate or adaptive immunity genes; including downregulation of IL1B and upregulation of IL1R2, reflecting suppression of innate immunity in GNB subjects. We also observed downregulation of adaptive immune genes in the GNB subjects. Conclusions By 96 hours after injury, there are differences in leukocyte gene expression associated with the development of GNB, reflecting suppression of both innate and adaptive immunity. GNB after trauma is, in part, consequence of host immunity failure and may not be completely preventable by standard infection-control techniques.

Sepsis Induces Specific Changes in Histone Modification Patterns in Human Monocytes

“…4 ). Remarkably, these results are in line with a very recent study in post-traumatic patients developing sepsis, which demonstrates a down-regulation of IL-1β as well as an up-regulation of IL1R2 gene expression and proposingg a suppression of innate immunity [ 25 ].…”

The immunosuppressive face of sepsis early on intensive care unit—A large-scale microarray meta-analysis

“…IL1-R2 is counteracting inflammation by binding IL-1beta without intracellular signaling transduction, and its gene expression has been reported earlier to be of high diagnostic usefulness for sepsis, also after trauma. [ 40 , 41 ] Similar results have been shown for inflammatory IL-18 and blocking it together with IL-1β protected animals against inflammation and shock. [ 42 ]…”

Postinjury Inflammation and Organ Dysfunction

“…An analysis of leukocyte gene expression associated with post-trauma Gram-negative bacteremia in the Glue Grant dataset showed that both innate and adaptive immunity appeared to be suppressed by 96 hours postinjury. 138 These findings suggested that immunostimulants, such as interferon-gamma, in patients with decreased immune gene expression, may be a promising therapeutic approach. GM-CSF was tested in small trauma populations and shown to counteract trauma-induced monocyte function depression while IFN-γ had the capacity to enhance HLA-DR on B and T lymphocytes.…”