The Hepatic Acute Phase Response to Thermal Injury

A thermal injury represents one of the most severe forms of trauma and occurs in over two million people in the United States of America per year (1). According to the World Health Organization (WHO), an estimated 330,000 deaths per year worldwide are related to thermal injury (2). Over 440,000 children receive medical attention for burn injuries each year in the United States (3). With approximately 1,100 children dying of burn-related injuries in the United States every year (4), severe burns represent the third most common cause of death in the pediatric patient population (5) and account for a significant number of hospital admissions in the United States (6, 7). A severe burn, therefore, represents a devastating injury affecting nearly every body organ system and leads to significant patient morbidity and mortality (8). Burn produces a profound hypermetabolic stress response characterized by increased glucose production via glycogenolysis and gluconeogenesis, lipolysis, and protein catabolism (7-9). The hypermetabolic stress response is driven by the inflammatory response, which encompasses hormones, cytokines, and acute phase proteins (10-12). Clinical studies have shown that sustained or increased hypermetabolic, inflammatory, and acute phase responses can be life threatening with the uncontrolled and prolonged action of counterregulatory stress hormones (cortisol, catecholamines, glucagon), cytokines and acute phase proteins contributing to multi-organ failure, hypermetabolism, hypercatabolism, morbidity, and mortality (11-13). Over the last two decades, burn research focused on areas such as hypermetabolism, resuscitation, wound healing, pulmonary support, and infection (7). Advances in these areas improved post-burn outcomes, but severe burn is still associated with significant morbidity and mortality. We are (14-17) proposing that an integral part of the post-burn response has not been determined and, therefore, focused our research on the role of the liver. The liver, with its metabolic, inflammatory, immune, and acute phase functions, plays a pivotal role in patient survival and recovery by modulating multiple pathways (13). The role of the liver during the post-burn response is essentially unknown and we, therefore, initiated a variety of studies to determine the function and role of the liver during the post-burn response. This review aims to discuss the liver and its role during the post-burn response.