Role of systemic hypothermia on inflammatory response and apoptosis in severe tissue injury

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Changes in body temperature occur during inflammation upon severe tissue injury, however the role of body temperature on inflammatory responses remains obscure. Thermoregulatory responses considerably vary from hypothermia to fever. Though hypothermic trauma patients seem to have a worse prognosis, there is the question whether it is the hypothermia per se or the severity of injury producing the hypothermia that is responsible for increased mortality. The proposed project focuses on how mild to moderate hypothermia modulates local and systemic inflammatory response and cell apoptosis upon tissue injury. Based on recent work of our group using the skinfold chamber model and high resolution multifluorescence microscopy in mice (FASEB J, 2002), we will assess microvascular, cellular and molecular events in severely injured tissue of p53+/+ and p53-/- mice with hypothermia (32°C-35°C), emphasising the role of low body temperature on the progress of p53-mediated apoptotic tissue death. Additionally, in vitro approaches using p53 wild-type and p53 mutant cells further allow us to study the effect of subnormal temperatures on cellular stress response. The proposed project should solve the controversy about the value of hypothermia in severe trauma, being either a simple marker of illness or a major contributor to disease.