Modulation of immune response by head injury Maria Cristina Morganti-Kossmann a,b,c , Laveniya Satgunaseelan a,b , Nicole Bye a,b , Thomas Kossmann a,b,c, * a Department of Trauma Surgery, The Alfred Hospital, Monash University, Commercial Road, Melbourne, Vic. 3004, Australia b National Trauma Research Institute, Monash University, Commercial Road, Melbourne, Vic. 3004, Australia c Monash University, Australia Accepted 3 October 2007 Despite longstanding statistics showing it to be the leading cause of morbidity and mortality in those under the age of 45 in the industrialised world, traumatic brain injury (TBI) is still a silently growing international epidemic. As developing countries become increasingly motorised, this is only set to increase. The World Health Organisation, in its 2004 World Report on Road Traffic Injury Prevention, found that by 2020, road traffic accidents would be within the top three leading causes of the global burden of disease, ahead of HIV and tuberculosis. 112 Injury, Int. J. Care Injured (2007) 38, 1392—1400 www.elsevier.com/locate/injury KEYWORDS Traumatic brain injury (TBI); Patients; Animal models; Neuroinflammation; Cytokines; Interleukins; Chemokines Summary Despite the fact that traumatic brain injury (TBI) is a silently growing epidemic, we are yet to understand its multifaceted pathogenesis, where various cellular pathways are initiated in response to both the primary mechanical insult and secondary physiologically mediated injury. Although the brain has traditionally been considered an immunologically privileged site, evidence to the contrary exists in studies of central nervous system (CNS) pathology, in particular TBI. Transmigration of leukocytes following blood brain barrier (BBB) disruption results in activation of resident cells of the CNS, such as microglia and astrocytes, to possess immunological function. Both infiltrating peripheral immune cells and activated resident cells subsequently engage in the intrathecal production of cytokines, important indicators of the presence of neuroinflammation. Cytokines can either promote this neurotoxi- city, by encouraging excitotoxicity and propagating the inflammatory response, or attenuate the damage through neuroprotective and neurotrophic mechanisms, including the induction of cell growth factors. Certain cytokines perform both functions, for example, interleukin-6 (IL-6). This review article discusses the notion that the inflammatory response to TBI is no longer a peripherally mediated phenom- enon, and that the CNS significantly influences the immunological sequence of events in the aftermath of injury. Crown Copyright # 2007 Published by Elsevier Ltd. All rights reserved. * Corresponding author at: Department of Trauma Surgery, National Trauma Research Institute, The Alfred Hospital/Monash University, Commercial Road, Melbourne, Vic. 3004, Australia. Tel.: +61 3 90762561; fax: +61 3 9076 3804. E-mail address: t.kossmann@alfred.org.au (T. Kossmann). 0020–1383/$ — see front matter. Crown Copyright # 2007 Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.injury.2007.10.005