Patrick Mulder

31 Review Immune Cells in Animal Burn Models Figure 3. Overall outcome of immune cell counts and function after burn injury. Overall metaanalysis of(A) blood immune cell counts, (B) blood lymphocyte counts, (C) wound immune cell counts, and (D) immune cell functions. Results are shown as SMD of immune cell counts in the blood or wound tissue from burn-injured animals compared with immune cell counts in blood or skin from uninjured animals (baseline or control group) ± CI95%. The I 2 statistic, number of studies, and the total number of animals used in the burn group for each meta-analysis are shown below the graphs. CI95%, 95% confidence interval; SMD, standardized mean difference. Blood innate response intensifies and is persistent We performed longitudinal analysis on selected time intervals encompassing the four different biological phases of wound healing: hemostasis, inflammation, proliferation, and remodeling (Figure 4A-G). Meta-regression analyses were performed from post burn day (PBD) 0 until PBD 21 (Figure 4H). Blood leukocytes displayed a steady increase, with the highest counts from PBD 5 until PBD 28 (Figure 4A). Neutrophil counts were immediately increased during injury and remained elevated up to PBDs 15‒21 (Figure 4B). Monocyte counts were increased from PBD 5 until PBD 14 (Figure 4C). Thrombocyte counts were decreased on PBDs 0‒1 and later increased on PBDs 5‒9 (Figure 4D). The decline of lymphocytes was most predominant directly after burn injury, whereas on PBDs 10‒14, counts returned to control levels (Figure 4E). We detected a decrease in B-cell counts on PBDs 5‒9 but found no significant differences in T-cell counts (Figure 4F,G). To further investigate the opposed dynamics of neutrophils and lymphocytes during burn injury, we calculated the neutrophil/lymphocyte ratio (NLR) for studies that reported both neutrophil and lymphocyte counts (Supplementary Figure 1). During the first 9 days, significantly higher NLRs were observed in burn-injured animals, which is an indication of systemic inflammatory response syndrome [10]. Overall, the temporal analysis revealed that whereas the increase in neutrophil counts was immediate, total 2

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