D. T. Lubkin1,6, M. Song1,6, M. Bishawi1,6, T. V. Brennan2, E. A. Elster3,4,6, A. D. Kirk1,5,6 1Duke University Medical Center,Surgery,Durham, NC, USA 2Cedars-Sinai Medical Center,Surgery,Los Angeles, CA, USA 3Walter Reed Army Medical Center,Washington, DC, USA 4Uniformed Services University Of The Health Sciences,Bethesda, MD, USA 5Duke University Medical Center,Immunology,Durham, NC, USA 6Uniformed Services University Of The Health Sciences,Surgical Critical Care Initiative (SC2i),Bethesda, MD, USA
Introduction: Systemic inflammatory response syndrome (SIRS) is a major cause of delayed morbidity and mortality in trauma patients and can result in hypoperfusion, organ failure, and death. Soluble CD154 (CD40 Ligand) is released by platelets activated in response to endothelial damage and may contribute to systemic inflammation through stimulation of CD40 on monocytes and endothelial cells, leading to release of interleukin-6 (IL-6), IL-8, and monocyte chemotactic protein 1 (MCP-1). The aim of this study was to investigate the association between plasma levels of soluble CD154 (sCD154) in trauma patients and the development of post-traumatic SIRS.
Methods: Samples and clinical data were prospectively collected from acutely injured patients as part of the Surgical Critical Care Initiative (SC2i). All samples were collected within 24 hr of injury. Plasma sCD154 levels were measured by enzyme-linked immunosorbent assay (ELISA) and serum IL-6, IL-8, and MCP-1 levels were measured by Luminex® assay.
Results: Of the 29 patients included, 15 (51.7%) developed SIRS and 14 (48.3%) did not. Median plasma sCD154 level was significantly higher in the SIRS group than in the no SIRS group [Median (IQR) 72.19 (63.78-116.4) vs. 55.72 (42.07-77.63) pg/ml, p=0.017]. Median serum IL-6 level was significantly higher in the SIRS group [SIRS: 78.73 (38.2-112.6) vs. no SIRS: 34.09 (17.36-47.41) pg/ml, p=0.018]. Median levels of IL-8 [34.45 (21.27-68.5) vs. 23.77 (8.64-54.89) pg/ml, p=0.16] and MCP-1 [508.1 (417.1-854.3) vs. 415.1 (228-680.7) pg/ml, p=0.38] trended higher in the SIRS group, but these differences did not reach statistical significance.
Conclusion: sCD154 levels are elevated in patients with clinical SIRS and thus may be useful as a biomarker, alone or in combination with other inflammatory cytokine levels. Further work is warranted to assess the role of sCD154 in the evolution of post-traumatic inflammatory responses, and its blockade as a potential therapeutic strategy for the prevention and treatment of SIRS.