Patrick Mulder

33 Review Immune Cells in Animal Burn Models and decreased neutrophil antibacterial activity on PBDs 5‒9 (Figure 5E-G). Macrophage numbers increased immediately and remained elevated until PBD 14 (Figure 5H). Release of inflammatory mediators by macrophages was increased on PBDs 0‒4 (Figure 5I). Altogether, the instant increase of innate immune cells in wound tissue persisted for at least 2 weeks, whereas certain functions were affected. Figure 5. Longitudinal analyses of wound immune cell counts and cell function after burn injury. Longitudinal meta-analysis of (A) burn wound leukocyte counts, (B) leukocyte migration, (C) burn wound mast cell counts, (D) burn wound neutrophil counts, (E) neutrophil antibacterial activity, (F) neutrophil ROS production, (G) neutrophil inflammatory mediator production, (H)burn wound macrophage counts, and (I) macrophage inflammatory mediator production. (J) Metaregression with the immediate effect (intercept) and linear coefficient of time after burn (PBD 0 until PBD 21). Results are shown as SMD of immune cell counts in wound tissue from burn-injured animals compared with immune cell counts in the skin from uninjured animals (baseline or control group) ± CI95%. The I 2 statistic, number of studies, and the total number of animals in the burn group for each interval are shown below the graphs. Bonferroni-corrected P-values of significant differences between intervals are given in the graphs. CI95%, 95% confidence interval; inflamm., inflammatory; med., mediator; NS, not significant; PBD, post burn day; prod., production; SMD, standardized mean difference. Immune response depends on animal characteristics and burn technique To investigate the differences between experimental models, subgroup analyses were performed (Figure 6). The highest blood leukocyte counts were found in rats or in adult animals. Sensitivity analyses confirmed that the interspecies effect was still present when only young animals were compared and that the difference from aging remained when only rats were analyzed. Neutrophil counts were higher in studies using >25% 2

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