Inflammation and Sepsis: Past, Present, and the Future

A critical burn injury is a unique trauma that often is accompanied by significant metabolic disturbances as well as perturbation of innate and adaptive immunity.1,2 Human skin is not only a barrier against environmental insults and against colonization of pathogenic microbes but, more importantly, it is an immune organ with significant surveillance and thermoregulatory functions.3 Therefore, it is hardly surprising that loss of large portions of skin as the result of burns results in impaired immunity, metabolic compromises, fluid shifts, and heat loss. Through improvements in resuscitation, critical care, nutritional support, and early closure of the burn wound during the past two decades, our ability to care for burn patients has resulted in a marked reduction in morbidity and mortality. However, nosocomial wound or pulmonary infections, especially in patients requiring ventilator assistance, remain a major problem. Inflammation is an essential and primordial component of normal healing when wounds are small and localized. Prompt wound closure resolves this response.4,5 However, inflammatory responses in a critical burn injury often are deranged because there is global involvement of multiple tissue beds and their constituent immune and nonimmune cells, placing significant metabolic and energy requirements on the repair process. For example, the extent of inflammation and energy requirements is directly proportional to the severity of injury sustained by the patient.6 The spectrum of inflammation runs from a mild elevation in cytokines associated with inflammation that largely go unnoticed clinically to a systemwide severe inflammatory response that eventually leads to microcirculatory failure of capillaries supplying individual vital organs, acute respiratory syndrome, severe coagulopathy, and the development of the multiple organ failure.