BACKGROUND: Transfusion-related immunomodulation consists of both proinflammatory and anti-inflammatory responses after transfusion of blood products. Stored red blood cells (RBCs) suppress human T-cell proliferation in vitro, but the mechanism remains unknown. We hypothesized that cytokine synthesis by T cells may be inhibited when stored RBCs are present and that suppression between fresh and stored RBCs would be different.
METHODS: Purified human T cells were stimulated to proliferate with anti-CD3/anti-CD28 and then exposed to stored or fresh RBCs. Cells were placed in culture for 5 days. Cell culture supernatants were analyzed for the production of typical T-cell cytokines using multianalyte ELISArray kits.
RESULTS: Stimulated T cells proliferated. RBC exposure markedly suppressed this proliferation. Interleukin 10, interleukin 17a, interferon γ, tumor necrosis factor α, and granulocyte macrophage colony-stimulating factor were increased in response to stimulation but depressed in the presence of stored RBCs. The use of fresh RBCs also resulted in depression of these cytokines when compared with stimulated T cells with no RBCs; however, this depression was less pronounced.
CONCLUSION: T-cell activation is associated with both proinflammatory and anti-inflammatory cytokine release, comparable with patterns seen in trauma and acute injury. All of these responses are depressed by an exposure to stored RBCs. Decreased levels of these cytokines after RBC transfusion represents a potential contributor to the immunosuppressive complications seen in trauma patients after transfusion. This provides insight for future mechanistic studies to delineate the role of RBC transfusion in transfusion-related immunomodulation.
From the Section on Trauma and Acute Care Surgery (L.P., C.M., A.B.), Division of General Surgery (K.L.), Department of Microbiology, Immunology and Molecular Genetics (J.W., M.W.), and Department of Pathology (D.W.), University of Kentucky, Lexington, Kentucky.
Submitted: December 9, 2013, Revised: April 21, 2014, Accepted: April 28, 2014.
This study was presented in the Raymond Alexander Paper Competition at the 27th Eastern Association for the Surgery of Trauma Annual Scientific Assembly, January 14–18, 2014, in Naples Florida.
Address for reprints: Kristin Long, MD, Department of General Surgery, University of Kentucky, 800 Rose St, Lexington KY 40536; email: Kristin.firstname.lastname@example.org.