The Immune Response to Skin Trauma Is Dependent on the Etiology of Injury in a Mouse Model of Burn and Excision

Abstract

Skin trauma has many different causes including incision, blunt force, and burn. All of these traumas trigger an immune response. However, it is currently unclear whether the immune response is specific to the etiology of the injury. This study was established to determine whether the immune response to excision and burn injury of equivalent extent was the same. Using a mouse model of a full-thickness 19 mm diameter excision or 19 mm diameter full-thickness burn injury, we examined the innate immune response at the level of serum cytokine induction, whole-blood lymphocyte populations, dendritic cell function/phenotype, and the ensuing adaptive immune responses of CD4 and CD8 T-cell populations. Strikingly, both the innate and adaptive immune system responses differed between the burn and excision injuries. Acute cytokine induction was faster and different in profile to that of excision injury, leading to changes in systemic monocyte and neutrophil levels. Differences in the immune profile between burn and excision were also noted up to day 84 post injury, suggesting that the etiology of injury leads to sustained changes in the response. This may in part underlie clinical observations of differences in patient morbidity and mortality in response to different skin injury types.

Burn Injury Leads to Increased Long-Term Susceptibility to Respiratory Infection in both Mouse Models and Population Studies

“…Advances in medical management in recent years have resulted in significant declines in hospital mortality,[5, 6]. However, population-based research has shown burn survivors experience decreased long-term survival [7, 8], whilst increased long-term morbidity has been shown both in population studies and other models of burn injury [9–11]. …”

“…More recently, we have shown that the etiology of injury is important, with even non-severe burn injury leading to sustained and unique changes in immune cell profiles in a murine model [11]. However, the consequences of these changes on morbidity in the longer term are currently unknown.…”

Flt3 Ligand Treatment Attenuates T Cell Dysfunction and Improves Survival in a Murine Model of Burn Wound Sepsis

“…Our major findings included a significant loss of the blood lymphocytes and splenic T cells following burn injury and associated sepsis. Studies from other laboratories have also shown that cutaneous causes a suppression of splenic T cell cytokine production (3). Burn injury has also been shown to induce T cell apoptosis (4), a decreased ability of T cells to proliferate upon polyclonal and antigen specific stimulation, and to secrete Th1 cytokines, including interferon-γ (5).…”

Long-term Effects of Pediatric Burns on the Circulatory System

“…8,13 Despite the absence of a hypermetabolic response, minor burns elicit a substantial acute inflammatory response. 9 It may be that this response in part mediates the profound long-term changes observed after minor burn injuries. 8 Although the incidence rate of admissions was elevated after severe burns, the lack of a significant association may be related to the small numbers of patients with severe burns in this patient cohort, the classification of TBSA used (,20% and $20%), and, potentially, that survivors of severe burns in this study represent a healthier patient subcohort.…”

“…2,5,7,8 These changes have been postulated to be mediated by the acute inflammatory response. 9 Understanding the long-term health effects of burns is of particular importance to young children, who have the highest incidence of burn injuries 10 and the longest time to be affected by any secondary pathology subsequent to burn injury. To date, limited data have been available to examine the long-term health effects of pediatric burns beyond 3 years postburn.…”