World J. Surg. 16, 30-36, 1992
O
World Journal of Surgery O 1992 by the Soei~t~ lntcmationale de Chirurgie
The Role of Mediators in the Response to Thermal Injury Y e o - K y u Y o u n , M.D., Cheryl L a L o n d e , B.S,, and Robert Demling, M.D. Longwood Area Trauma/Burn Center at Harvard Medical School, Boston, Massachusetts, U.S.A. and Seoul National University Hospital, Seoul, Korea Inflammatory mediators play a major role in both the local burn wound and the systemic response to burn injury. Oxidant and arachidonic acid metabolites are involved in the initial burn edema process. The mediators as well as the cytokines released from activated macrophages also result in an early generalized inflammatory response. The later postburn hypermetabolism is initiated and perpetuated by these same mediators, especially the cytokines, tumor necrosis factor, interleukin-l, and interleukin-2. Circulating endotoxin from the wound or the gut also appears to be involved. The postburn septic response is now recognized to be the result of inflammation; infection is not necessary. Mediator induced priming of the inflammatory cells by the burn itself results in an exaggerated response to infection in the postburn period. Defining the specific mechanism of injury and mediators involved can result in a major improvement in burn care, especially since many mediator inhibitors are already available for clinical use. It is essential that the clinician understand this pharmacologic manipulation in order to be able to optimally utilize these future advances.
It is becoming increasingly clear that there is a massive systemic inflammatory response to local tissue trauma, especially a skin burn [!-4]. Although the inflammation is initiated almost immediately after injury, the systemic response progresses with time, usually peaking 5 days to 7 days after the burn injury. This response is evidenced by marked hypermetabolism and an accentuated response to any subsequent insult, especially infection [5-7]. Although much of the postburn mortality and morbidity is almost certainly related to infection, it is the amplified response of the burn patient to bacteria and bacterial by-products, in particular endotoxin, which produces the actual tissue damage and hemodynamic instability [5-7]. The response to the initial burn injury and the presence of the burn wound are now well recognized to prime the host for a subsequent insult. Early burn wound removal decreases the later response, indicating the importance of the wound in this process [8, 9]. This concept of postburn inflammation induced disease is of considerable importance in understanding burn induced disease and essential for designing appropriate prevention and treatment modalities. Several recent clinical studies in trauma patients have veriReprint requests: Robert H. Demling, M.D., Longwood Area Trauma Center, 75 Francis Street, Boston, Massachusetts 02115, U.S.A.
fled that infection can be considered to initiate sepsis and subsequent organ dysfunction in
O
World Journal of Surgery O 1992 by the Soei~t~ lntcmationale de Chirurgie
The Role of Mediators in the Response to Thermal Injury Y e o - K y u Y o u n , M.D., Cheryl L a L o n d e , B.S,, and Robert Demling, M.D. Longwood Area Trauma/Burn Center at Harvard Medical School, Boston, Massachusetts, U.S.A. and Seoul National University Hospital, Seoul, Korea Inflammatory mediators play a major role in both the local burn wound and the systemic response to burn injury. Oxidant and arachidonic acid metabolites are involved in the initial burn edema process. The mediators as well as the cytokines released from activated macrophages also result in an early generalized inflammatory response. The later postburn hypermetabolism is initiated and perpetuated by these same mediators, especially the cytokines, tumor necrosis factor, interleukin-l, and interleukin-2. Circulating endotoxin from the wound or the gut also appears to be involved. The postburn septic response is now recognized to be the result of inflammation; infection is not necessary. Mediator induced priming of the inflammatory cells by the burn itself results in an exaggerated response to infection in the postburn period. Defining the specific mechanism of injury and mediators involved can result in a major improvement in burn care, especially since many mediator inhibitors are already available for clinical use. It is essential that the clinician understand this pharmacologic manipulation in order to be able to optimally utilize these future advances.
It is becoming increasingly clear that there is a massive systemic inflammatory response to local tissue trauma, especially a skin burn [!-4]. Although the inflammation is initiated almost immediately after injury, the systemic response progresses with time, usually peaking 5 days to 7 days after the burn injury. This response is evidenced by marked hypermetabolism and an accentuated response to any subsequent insult, especially infection [5-7]. Although much of the postburn mortality and morbidity is almost certainly related to infection, it is the amplified response of the burn patient to bacteria and bacterial by-products, in particular endotoxin, which produces the actual tissue damage and hemodynamic instability [5-7]. The response to the initial burn injury and the presence of the burn wound are now well recognized to prime the host for a subsequent insult. Early burn wound removal decreases the later response, indicating the importance of the wound in this process [8, 9]. This concept of postburn inflammation induced disease is of considerable importance in understanding burn induced disease and essential for designing appropriate prevention and treatment modalities. Several recent clinical studies in trauma patients have veriReprint requests: Robert H. Demling, M.D., Longwood Area Trauma Center, 75 Francis Street, Boston, Massachusetts 02115, U.S.A.
fled that infection can be considered to initiate sepsis and subsequent organ dysfunction in
