249 General Discussion Table 1. List of potential strategies to re-establish the balance after immune dysfunction instigated by burn injury. This list is not complete, but proposes several options that might be useful for the improvement of therapy. Aspect of burn injury Potential target Potential strategies Inflammatory triggers DAMPs Blockade of DAMPs: [132] Early debridement of burn tissue: [136,142,143] Inflammatory mediators Haemofiltration to remove cytokines: [130] Blockade of specific cytokines: [132,137,144] Blockade of chemokines: [137] Use of glucocorticoids: [133,134] Neutrophil response Neutrophil recruitment Blockade of chemokine signaling: [145] Neutrophil activity Suppress protease activity: [55] Neutrophil apoptosis Cyclin-dependent kinase inhibitors: [146] Macrophage response M1 macrophage activity Suppress M1 differentiation: [69] M2 macrophage activity Enhance M2 differentiation: [69,74,147] Lymphocyte response Pro-inflammatory activity Suppress Th1/Th17 response: [148] Anti-inflammatory activity Enhance Th2/Treg response: [26,149] Immune paralysis Restore immune function Checkpoint inhibition: [141] CONCLUSIONS Altogether, this thesis provides valuable insights into immune dysfunction after burn injury, while supporting the reduction of animal experimentation. We showed evidence that the response of innate immune cells is excessive and that adaptive immunity might be delayed and impaired, leading to long-lasting inflammation. Burn patients are likely to benefit from a timely restoration of their immune balance. Multiple approaches to achieve this have been proposed and discussed, paving the way for novel and more personalized treatment strategies. Future burn care will need more sophisticated and refined research models, collaborations between different disciplines, and validated biomarkers to predict clinical courses for safe application of therapies that timely restore the immune balance and support healing. 8
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