The systemic immune response to trauma: an overview of pathophysiology and treatment.
Improvements in the control of haemorrhage after trauma have resulted in the survival of many people who would otherwise have died from the initial loss of blood. However, the danger is not over once bleeding has been arrested and blood pressure restored. Two-thirds of patients who die following major trauma now do so as a result of causes other than exsanguination. Trauma evokes a systemic reaction that includes an acute, non-specific, immune response associated, paradoxically, with reduced resistance to infection. The result is damage to multiple organs caused by the initial cascade of inflammation aggravated by subsequent sepsis to which the body has become susceptible. This Series examines the biological mechanisms and clinical implications of the cascade of events caused by large-scale trauma that leads to multiorgan failure and death, despite the stemming of blood loss. Furthermore, the stark and robust epidemiological finding--namely, that age has a profound influence on the chances of surviving trauma irrespective of the nature and severity of the injury--will be explored. Advances in our understanding of the inflammatory response to trauma, the impact of ageing on this response, and how this information has led to new and emerging treatments aimed at combating immune dysregulation and reduced immunity after injury will also be discussed.
MRC-ARUK Centre for Musculoskeletal Ageing Research, School of Immunity and Infection, University of Birmingham, Birmingham, UK; NIHR Surgical Reconstruction and Microbiology Research Centre, University of Birmingham, Birmingham, UK.
Janet M
JM
Lord
NIHR Surgical Reconstruction and Microbiology Research Centre, University of Birmingham, Birmingham, UK; School of Health and Population Sciences, University of Birmingham, Birmingham, UK.
Mark J
MJ
Midwinter
NIHR Surgical Reconstruction and Microbiology Research Centre, University of Birmingham, Birmingham, UK; School of Health and Population Sciences, University of Birmingham, Birmingham, UK; Division of Health Sciences, University of Warwick, Coventry, UK.
Yen-Fu
YF
Chen
NIHR Surgical Reconstruction and Microbiology Research Centre, University of Birmingham, Birmingham, UK; Neurotrauma and Neurodegeneration Section, University of Birmingham, Birmingham, UK.
Antonio
A
Belli
Centre for Trauma Sciences, Blizard Institute, Queen Mary University of London, London, UK.
Karim
K
Brohi
Loyola University Chicago Health Sciences Campus, Stritch School of Medicine, Department of Surgery, Burn and Shock Trauma Institute, Maywood, IL, USA.
Elizabeth J
EJ
Kovacs
University Medical Centre Utrecht, Department of Respiratory Medicine, Utrecht, Netherlands.
Leo
L
Koenderman
University of Calgary, Department of Physiology and Pharmacology, Calvin Phoebe and Joan Snyder Institute for Chronic Disease, Calgary, Canada.
Paul
P
Kubes
School of Health and Population Sciences, University of Birmingham, Birmingham, UK; Division of Health Sciences, University of Warwick, Coventry, UK. Electronic address: R.J.Lilford@warwick.ac.uk.
Richard J
RJ
Lilford
D000367:Age Factors; D004703:Endocrine System / Q000276:immunology; D006487:Hemostasis / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D009504:Neutrophils / Q000276:immunology; D012737:Sex Factors; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000276:immunology / Q000628:therapy; D014947:Wounds and Injuries / Q000150:complications / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy