Callie M Thompson1, Chin H Park, Ronald V Maier, Grant E O'Keefe. 1. 1Division of Trauma and Burn Surgery, University of Washington/Harborview Medical Center, Seattle, WA. 2Department of General Surgery, Brookdale University Hospital and Medical Center, Brooklyn, NY.
Abstract
OBJECTIVES: Bacteremic trauma victims have a higher risk of death than their nonbacteremic counterparts. The role that altered immunity plays in the development of bacteremia is unknown. Using an existing dataset, we sought to determine if differences in early postinjury immune-related gene expression are associated with subsequent Gram-negative bacteremia. DESIGN: Retrospective cohort study, a secondary analysis of the Glue Grant database. SETTING: Seven level I trauma centers across the United State. SUBJECTS: Severely injured blunt trauma patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total leukocyte gene expression was compared between the subjects in whom Gram-negative bacteremia developed and those in whom it did not develop. We observed that Gram-negative bacteremia was an independent risk factor for death (odds ratio, 1.86; p = 0.015). We then compared gene expression at 12 and 96 hours after injury in 10 subjects in whom subsequently Gram-negative bacteremia developed matched to 26 subjects in whom it did not develop. At 12 hours, expression of 64 probes differed more than or equal to 1.5-fold; none represented genes related to innate or adaptive immunity. By 96 hours, 102 probes were differentially expressed with 20 representing 15 innate or adaptive immunity genes, including down-regulation of IL1B and up-regulation of IL1R2, reflecting suppression of innate immunity in Gram-negative bacteremia subjects. We also observed down-regulation of adaptive immune genes in the Gram-negative bacteremia subjects. CONCLUSIONS: By 96 hours after injury, there are differences in leukocyte gene expression associated with the development of Gram-negative bacteremia, reflecting suppression of both innate and adaptive immunity. Gram-negative bacteremia after trauma is, in part, consequence of host immunity failure and may not be completely preventable by standard infection-control techniques.
OBJECTIVES:Bacteremic trauma victims have a higher risk of death than their nonbacteremic counterparts. The role that altered immunity plays in the development of bacteremia is unknown. Using an existing dataset, we sought to determine if differences in early postinjury immune-related gene expression are associated with subsequent Gram-negative bacteremia. DESIGN: Retrospective cohort study, a secondary analysis of the Glue Grant database. SETTING: Seven level I trauma centers across the United State. SUBJECTS: Severely injured blunt traumapatients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total leukocyte gene expression was compared between the subjects in whom Gram-negative bacteremia developed and those in whom it did not develop. We observed that Gram-negative bacteremia was an independent risk factor for death (odds ratio, 1.86; p = 0.015). We then compared gene expression at 12 and 96 hours after injury in 10 subjects in whom subsequently Gram-negative bacteremia developed matched to 26 subjects in whom it did not develop. At 12 hours, expression of 64 probes differed more than or equal to 1.5-fold; none represented genes related to innate or adaptive immunity. By 96 hours, 102 probes were differentially expressed with 20 representing 15 innate or adaptive immunity genes, including down-regulation of IL1B and up-regulation of IL1R2, reflecting suppression of innate immunity in Gram-negative bacteremia subjects. We also observed down-regulation of adaptive immune genes in the Gram-negative bacteremia subjects. CONCLUSIONS: By 96 hours after injury, there are differences in leukocyte gene expression associated with the development of Gram-negative bacteremia, reflecting suppression of both innate and adaptive immunity. Gram-negative bacteremia after trauma is, in part, consequence of host immunity failure and may not be completely preventable by standard infection-control techniques.
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