The Local and Systemic Inflammatory Response in a Pig Burn Wound Model With a Pivotal Role for Complement

Abstract

In patients with burns, a massive inflammatory response is induced which negatively affects the healing process of the burn wound and additionally exerts systemic effects. An important factor herein is the complement system. Here we analyzed the effects of burns on complement and inflammatory cells both locally and systemically after burn in time in a pig burn wound model. In burned pigs, burn wound biopsies and blood were collected up to 60 days after burn. Complement in blood as well as complement and inflammatory cells in the burn wound and several organs were determined. In the blood, C3 was significantly increased after 9 to 60 days, whereas C4 after 21 to 30 days after burn. In the burn wound, C3 levels were significantly increased after 9 days and C4 after 3 days, whereafter both declined after 21 and 9 days, respectively. Neutrophils, macrophages, and lymphocytes were significantly increased in the burn wound after 3 days, all declined after 21 days after burn. In the heart, at 60 days after burn, an increase of neutrophils and macrophages was observed, mainly in the right atrium. In contrast to the heart, the inflammatory cell infiltrates in the lungs, liver, and kidney of burned pigs were lower than in control pigs. In pigs, following burn there is a prolonged increase in complement levels both in the burn wound and the blood and increased inflammatory cell infiltrate in the burn wound and the heart. However, complement levels in the burn wound and in the blood seem not to be correlated in time.

Neutrophil extracellular traps coincide with a pro‐coagulant status of microcirculatory endothelium in burn wounds

“…The microvascular thrombosis and NETosis we observed 14 days after burn trauma in rats were also observed in a prolonged episode up to 60 days in the pig burn wound model and in patients, suggesting that microvascular thrombosis and NETosis may play a pathogenic role in burn wound for an extended period of time. In line with this, we and others have observed previously that large numbers of neutrophils remain present in the burn wound up to weeks after trauma …”

“…In line with this, we and others have observed previously that large numbers of neutrophils remain present in the burn wound up to weeks after trauma. 5,16 Neutrophils are important in the antibacterial defense. However, their activation also results in the production of proinflammatory cytokines and ROS which may damage skin and microvascular endothelial cells and enhance ischemic tissue necrosis.…”

“…In order to study the different parameters in time, we used tissue samples from a porcine experiment …”

“…15 In vivo pig burn wound model In order to study the different parameters in time, we used tissue samples from a porcine experiment. 16 Three-month-old female Yorkshire pigs (n 5 7), weighing approximately 30 kg at arrival, were acclimatized for 1 week prior to the experiment. During the whole study, the pigs were individually housed and fed twice daily, with ad libitum access to water.…”

“…The burn wound procedures used in the three pigs we previously described in detail. 16 Briefly, eight (four wounds on each flank) dorsal full-thickness burns of 4 3 4 cm burned area (6 1.5% total body surface area [TBSA]) were created using a heated copper device (170 8C) during 20 seconds. The wounds were covered with wound dressing sterile gauzes, which were kept in place by adhesive bandage and elastic stockings.…”