120 Chapter 4 In burn trauma, the coordinated immune response is distorted and extended. A burninduced hyperinflammatory state is accompanied by significant elevation of immune cells, cytokines, and acute phase proteins [9]. Particularly serum interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor and monocyte chemoattractant protein (MCP)-1 revealed dramatic increases in a large set of severely burned (pediatric) patients [5,9]. These increases in cytokine levels were dependent on the size of the injury at 24–48 h after trauma [5]. In response to thermal injury, there is a rapid increase in bone marrowderived endothelial progenitor cells in peripheral blood, which correlates with the extent of injury [21]. In order to improve wound healing and limit the formation of hypertrophic scars, an improved understanding of the immune response induced by severe trauma is needed. This knowledge, together with clinical perspectives, could be used to resolve an excessive immune response by therapy to restore the immune balance and optimize wound healing. Although the time-course of cytokines due to burns has been reported [5,9,22], data on immune cells were not included. Our aim was to characterize the inflammatory response by investigating peripheral blood changes in subsets of innate and adaptive immune cells in time (post burn day (PBD) 0–39) and 33 inflammatory mediators (PBD 0–48) in adult patients with severe burn injury. RESULTS Systemic Inflammation After Burn Injury is Associated With Prolonged Increase of Peripheral Blood Granulocytes and Monocytes To examine the immune profile of burn wound patients in more detail, we performed multiparameter phenotyping by flow cytometry of peripheral blood of 20 burn wound patients up to 39 days after burn injury. All burn patients in the cohort showed signs of systemic inflammation (Supplementary Figure 2). Immediately after burn injury, total blood leukocyte counts were significantly increased compared to healthy controls. To analyze the response in time, a linear mixed model analysis was performed to determine the changes in comparison to time interval PBD 0–3. Data of PBD 0–3 was available for 15 patients. This analysis showed an additional increase in leukocyte counts until PBD 19–21 with the exception of PBD 13–15 (Figure 1A). Subtype analysis revealed that this increase of blood leukocytes could be ascribed to granulocyte and monocyte numbers, and not to lymphocyte counts (Figures 1B-D). In burn patients, granulocyte and monocyte counts rose significantly immediately after the injury compared to healthy controls but remained stable during the total time course (Figure 1B,D). Lymphocyte counts showed no increase compared to healthy controls. A small decrease around PBD 4–6 compared to PBD 0–3 was seen, followed by a non-significant tendency toward higher lymphocyte
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