Modulation of immune response by head injury.
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 neurotoxicity, 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 phenomenon, and that the CNS significantly influences the immunological sequence of events in the aftermath of injury.
Morganti-Kossmann
Maria Cristina
MC
Department of Trauma Surgery, The Alfred Hospital, Monash University, Commercial Road, Melbourne, Vic. 3004, Australia.
Satgunaseelan
Laveniya
L
Bye
Nicole
N
Kossmann
Thomas
T
D001930:Brain Injuries / Q000276:immunology*; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D018836:Inflammation Mediators / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D015213:Neuroimmunomodulation / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha