Abstract
BackgroundSevere trauma can induce pathophysiological responses that have marked inflammatory components. The development of systemic inflammation following severe thermal injury has been implicated in immune dysfunction, delayed wound healing, multi-system organ failure and increased mortality.MethodsIn this study, we examined the impact of thermal injury-induced systemic inflammation on the healing response of a secondary wound in the MRL/MpJ mouse model, which was anatomically remote from the primary site of trauma, a wound that typically undergoes scarless healing in this specific strain. Ear-hole wounds in MRL/MpJ mice have previously displayed accelerated healing and tissue regeneration in the absence of a secondary insult.ResultsSevere thermal injury in addition to distal ear-hole wounds induced marked local and systemic inflammatory responses in the lungs and significantly augmented the expression of inflammatory mediators in the ear tissue. By day 14, 61% of the ear-hole wounds from thermally injured mice demonstrated extensive inflammation with marked inflammatory cell infiltration, extensive ulceration, and various level of necrosis to the point where a large percentage (38%) had to be euthanized early during the study due to extensive necrosis, inflammation and ear deformation. By day 35, ear-hole wounds in mice not subjected to thermal injury were completely closed, while the ear-hole wounds in thermally injured mice exhibited less inflammation and necrosis and only closed partially (62%). Thermal injury resulted in marked increases in serum levels of IL-6, TNFα, KC (CXCL1), and MIP-2α (CXCL2). Interestingly, attenuated early ear wound healing in the thermally injured mouse resulted in incomplete tissue regeneration in addition to a marked inflammatory response, as evidenced by the histological appearance of the wound and increased transcription of potent inflammatory mediators.ConclusionThese findings suggest that the observed systemic inflammatory response of a severe thermal injury undoubtedly has an adverse effect on wound healing and tissue regeneration.
Highlights
Severe trauma can induce pathophysiological responses that have marked inflammatory components
Systemic inflammation can lead to profound suppression of the innate and adaptive immune system [4,5,6,7,8] resulting in increased sepsis, wound healing complications, multi-system organ failure, and remote organ injury at sites such as the lung, liver, small intestines, and brain, representing major causes of morbidity and mortality in burn trauma patients [3,9]
Impaired ear-hole wound closure in the MRL/MpJ mouse following a severe thermal injury at a remote injury site Full-thickness ear-hole biopsies were made in the pinnae of both ears within 1 hr after burn wounds (~177 mm2) were created on the mid-dorsum of each mouse
Summary
Severe trauma can induce pathophysiological responses that have marked inflammatory components. Systemic inflammation can lead to profound suppression of the innate and adaptive immune system [4,5,6,7,8] resulting in increased sepsis, wound healing complications, multi-system organ failure, and remote organ injury at sites such as the lung, liver, small intestines, and brain, representing major causes of morbidity and mortality in burn trauma patients [3,9] These thermally induced organ injuries appear to be caused by toxic inflammatory mediators produced by infiltrating activated neutrophils early after thermal injury that are associated with increased chemokine levels [10,11,12,13]. The interplay between pro- and anti-inflammatory mechanisms is key for avoiding further tissue damage beyond that of the primary insult and a systemic inflammatory response [4,68,13,16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
