Cytokines in stored red blood cell concentrates: promoters of systemic inflammation and simulators of acute transfusion reactions?

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Abstract
The cytokine network has important implications for the systemic inflammatory and metabolic response in trauma and infection. Cytokines exogenously administered to traumatized and infected patients may have implications for the trauma response in these patients. The main objective of this study was to characterize red blood cell concentrates (RBCs) with regard to cytokine content. We investigated the concentrations of tumor necrosis factor alpha (TNF), interleukin-1 beta (IL-1), interleukin-6 (IL-6) and interleukin-8 (IL-8) in sixteen units of RBCs stored at +4 degrees C during 40 days. Samples from RBCs were taken every tenth day. Healthy volunteers were used as controls. IL-1 and IL-8 in RBCs were increased compared to controls, P < 0.01 - P < 0.001 and TNF in RBCs were increased on days 1 and 40 compared to controls, P < 0.05. During storage TNF was highest on day 1, 69 (< 3-1060) pg/ml, median (range). IL-1 concentrations increased during the period of storage from 5 (< 2 - 205) pg/ml to 174 (< 2 - 2180) pg/ml, P < 0.01. IL-6 was 6 (< 2 - 210) pg/ml on day 1 and did not change over the period of storage. IL-8 was highest on day 40, 164 (15 - 790) pg/ml and compared to day 1 the concentrations were increased on day 10 and day 40, P < 0.05 for both comparisons. The results indicate the presence of TNF, IL-1, IL-6 and IL-8 in stored RBCs, though there was a great variability over the period of storage and between units of RBCs. In some samples of RBCs the content of cytokines reached levels that may be anticipated to contribute to systemic inflammation and the symptomatology of acute transfusion reactions.