A genomic storm in critically injured humans

Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and show that the severe stress produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected “genomic storm.” In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. Blood was sampled from 167 severe blunt trauma patients under the age of 55 yr who consented to blood sampling. The first blood sample was taken within 12 h of the injury and 1, 4, 7, 14, 21, and 28 d after injury. Study subjects were treated under the guidance of standard operating procedures developed, implemented, and audited across all participating centers to minimize treatment variation. In addition, 37 healthy control subjects were sampled. Total blood leukocytes were isolated according to protocols published previously. Total cellular RNA was extracted and hybridized onto an HU133 Plus 2.0 GeneChip (Affymetrix) according to the manufacturer’s recommendations.