37 Review Immune Cells in Animal Burn Models surrounding tissues, thereby producing additional danger-associated molecular patterns and cytokines that uphold the inflammation. The time-dependent response of thrombocytes is similar to the early thrombocyte response in burn patients [20]. The typical early trauma-induced leukopenia in patients with burn wounds that is caused by exsanguination, resuscitation, and emigration of immune cells from the blood circulation was in our meta-analysis only visible when the early time points were analyzed per day. Leukopenia is naturally restored by the bone marrow [21,22]. During acute inflammation, predominantly, neutrophils and monocytes are replenished by the bone marrow, which can lead to reduced lymphopoiesis and overrepresentation of innate immune cells in the circulation [23]. Moreover, the NLR, a marker for systemic inflammatory response syndrome in humans, was in animals also highly increased during the first 9 days after burns. In patients with burns, persistent leukocytosis in combination with lymphopenia is associated with persistent inflammation, arrested wound healing, increased susceptibility to opportunistic infection, and increased mortality [2,24,25]. Because the thrombocyte count and NLR correspond with systemic inflammatory response syndrome and septic events, they are of prognostic and diagnostic value [10,26]. In wound tissue of animals, increased levels of neutrophils, macrophages, and mast cells were detected until at least PBD 14. The transition of macrophages from an M1 phenotype toward an M2 phenotype is essential to facilitate proper wound healing [27,28]. Although monocyte or macrophage subtypes could not be investigated, we found that total wound macrophage numbers were increased and that the production of inflammatory mediators by macrophages was enhanced. The activity of neutrophils is altered after severe trauma in animals [29–32], but it remains unclear whether trauma, in general, enhances or weakens neutrophil activity (Figure 5). Presumably, the emergency release of neutrophils into the circulation is responsible for reduced chemotactic activity owing to the inflexibility of the banded nucleus of immature neutrophils [33], whereas rapid activation can lead to impaired antibacterial activity [31]. On the other hand, the immaturity of neutrophils could amplify the granule content and increase the release of inflammatory factors [34,35]. Mast cells have also been proposed to play an active role during wound healing in both animals and humans. They might enhance inflammation and vascular permeability through the secretion of histamines early after injury and stimulate re-epithelization and angiogenesis later on by the release of GFs [36,37]. This coincides with increased numbers of mast cells on PBDs 0‒1 and on PBDs 15‒21. Only a minority of studies used porcine or canine models, and therefore it was unfeasible to study the differences between species other than mice and rats. Although pigs come 2
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