15 General Introduction DISTORTED WOUND HEALING DURING BURN INJURY During wound healing, the immune homeostasis and tissue repair processes are usually tightly controlled to avoid collateral damage and to ensure a timely recovery [49–51]. Because burn injury often destroys a large portion of skin, it creates a large area of necrotic tissue that can cause an overstimulation of the immune system [27,52]. Fibroblasts, keratinocytes and innate immune cells are highly responsive and release extremely high levels of cytokines that in turn attract massive amounts of inflammatory cells. Extreme influx of pro-inflammatory immune cells can lead to expansion of the wound area, thereby producing additional inflammatory signals [29,53]. Eventually, this can become in a vicious circle of inflammation that will impede tissue repair (Figure 2). Figure 2. Vicious circle of inflammation and tissue damage that can establish after burn injury. During the inflammatory phase after trauma, immune cells will migrate into the wounded skin to remove debris and prevent bacterial colonization [38]. Within days, a portion of these cells disappear through apoptosis while others differentiate into a state that supports wound healing [49]. Generally within one week after injury, lymphocytes will infiltrate the wound site to regulate any ongoing inflammation and, if required, orchestrate a tailored effector response to eliminate infiltrated pathogens [54]. Following the effector phase, reduction of the immune response is needed to establish a proper wound healing process. This will shift the focus from inflammation towards 1
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