Abstract
Background
Based on the known inflammatory role of interleukins (IL), we evaluated IL-1β and IL-6 expressions and their association with the severity of traumatic brain injury (TBI; Glasgow Coma Scale [GCS]) and the outcome (Glasgow Outcome Score [GOS]) recorded in a paediatric population.
Design
The design was a perspective observational clinical study carried out in the paediatric intensive care unit of the University Hospital.
Methods
We measured the IL-1β and IL-6 levels in 14 children with severe TBI (patients) and in 12 children with obstructive hydrocephalus (control group). Cerebrospinal fluid (CSF) and plasma samples were collected 2 h (T1) and 24 h (T2) after TBI. Interleukins were assayed using the immunoenzymatic method.
Results
The IL-1β mean level was significantly lower than the IL-6 mean level both in the CSF and plasma of TBI children. In the CSF, the IL-1β level increased from 55.71±72.79 pg/ml at T1 to 106.10±142.12 pg/ml at T2 and the IL-6 level increased from 405.43±280.28 pg/ml at T1 to 631.57±385.35 pg/ml at T2; a similar trend was observed in plasma. We found a statistically significant correlation between the increase in CSF and plasma interleukin levels between T1 and T2 and head injury severity (GCS≤5) as well as poor outcome (GOS≤3).
Conclusions
The increases in IL-1β and IL-6 expression were correlated with head injury severity and were indicative of poor clinical outcome, reflecting an endogenous neuroinflammatory response after TBI.
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References
Alderson P, Roberts I (1997) Corticosteroids in acute traumatic brain injury: systematic review of randomized controlled trial. Br Med J 314:1855–1859
Amick JE, Yandora KA, Bell MJ (2001) The Th1 versus Th2 cytokine profile in cerebrospinal fluid after severe traumatic brain injury in infants and children. Pediatr Crit Care Med 2:260–264
Baggiolini M, Dewald B, Moser B (1997) Human chemokines: an update. Annu Rev Immunol 15:675–705
Bell MJ, Kochanek PM, Doughty LA, Carcillo JA, Adelson PD, Clark RS, Wisniewski SR, Whalen MJ, DeKosky ST (1997) Interleukin 6 and interleukin-10 in cerebrospinal fluid after severe traumatic brain injury in children. J Neurotrauma 14:451–457
Bell MJ, Sinz E, Kochanek PM, Doughty LA (1998) Quinolinic acid in cerebrospinal fluid of children after traumatic brain injury: a preliminary report. Crit Care Med 26:A86
Bona E, Anderson AL, Blomgrunk C (1999) Chemokines and inflammatory cell response to hypoxia ischemia in immature rats. Pediatr Res 45:500–509
Chao CC, Hu S, Ehrlich L, Peterson PK (1995) Interleukin 1 and TNFα synergistically mediate neurotoxicity: involvement of nitric oxide and of NMDA receptors. Brain Behav Immun 9:355–367
Clark RS, Schiding JK, Kaczorowosky SL, Marion DW, Kochanek PM (1994) Neutrophil accumulation after traumatic brain injury in rats: comparison of weight drop and controlled cortical impact models. J Neurotrauma 11:499–506
Donnelly SC, Strieter RM, Kunkel SL, Walz A, Robertson CR, Carter DC, Grant IS, Pollok AJ, Haslett C (1993) Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups. Lancet 341:643–647
Fassbender K, Schmincke U, Ragoschkle A, Kischka U, Fatar M, Hennerici M (1997) Endothelial-derived adhesion molecules in bacterial meningitis: association to cytokine release and intrathecal leukocyte recruitment. J Neuroimmunol 74:130–134
Fassbender K, Schneider S, Bertsch T, Schlueter D, Fatar M, Ragoschke A, Kuhl S, Kischka U, Hennerici M (2000) Temporal profile of release of interleukin-1β in neurotrauma. Neurosci Lett 284:135–138
Gilles FA, Averill D, Kerr S (1977) Neonatal endotoxin encephalopathy. Ann Neurol 2:49–56
Giulian D, Lachman LB (1985) Interleukin-1 stimulation of astroglial proliferation after brain injury. Science 228:497–499
Goss JR, Styren SD, Miller PD, Kochanek PM, Palmer AM, Marion DW, DeKosky ST (1995) Hypothermia attenuates the normal increase in interleukin 1 beta RNA and nerve growth factor following traumatic brain injury in the rat. J Neurotrauma 12:159–167
Gupta AK, Thiru S, Bradley J (1995) Delayed increases in adhesion molecule expression after traumatic brain injury in humans: preliminary results. J Cereb Blood Flow Metab 15:S33
Hack CE, Hart M, van Schijndel RJ, Eerenberg AJ, Nuijens JH, Thijs LG, Aarden LA (1992) Interleukin-8 in sepsis: relation to shock and inflammatory mediators. Infect Immun 60:2835–2842
Hama T, Miyamoto M, Tsukui H, Nishio C, Hatanaka H (1989) Interleukin-6 as a neurotrophic factor for promoting the survival of cultured basal forebrain cholinergic neurons from postnatal rats. Neurosci Lett 104:340–344
Hangberg H, Gilliaud E, Bona E (1999) Enhanced expression of IL-1 and IL-6 m-RNA and bioactive protein after hypoxia ischemia in neonatal rats. Pediatr Res 40:603–609
Hariri RJ, Chang VA, Barie PS, Wang RS, Sharif SF, Ghajar JBG (1994) Traumatic injury induces interleukin-6 production by human astrocytes. Brain Res 636:139–142
Herx LM, Rivest S, Yong VW (2000) Central nervous system-initiated inflammation and neurotrophism in trauma: IL-1β is required for the production of ciliary neurotrophic factor. J Immunol 165:2232–2239
Hodge CJ, Boakye M (2001) Biological plasticity: the future of science in neurosurgery. Neurosurgery 48:2–16
Jeohn GH, Kong LY, Wilson B, Hudson P, Hong JS (1998) Synergistic neurotoxic effects of combined treatments with cytokines in murine primary neuron/glia cultures. J Neuroimmunol 85:1–10
Kaczorowsky SL, Schiding JK, Toth CA et al (1995) Effect of soluble complement receptor-1 on neutrophil accumulation after traumatic brain injury in rats. J Cereb Blood Flow Metab 15:860–864
Kalabalikis P, Papazoglou K, Gouriotis D, Papadopoulos N, Kardara M, Papageorgiou F, Papadatos J (1999) Correlation between serum IL-6 and CRP levels and severity of head injury in children. Intensive Care Med 25:288–292
Kossmann T, Hans V, Imhof HG, Trentz O, Morganti-Kossmann MC (1996) Interleukin-6 released in human cerebrospinal fluid following traumatic brain injury may trigger nerve growth factor production in astrocytes. Brain Res 713:143–152
Kossmann T, Stahel PF, Lenzlinger PM, Redl H, Dubs RW, Trentz O, Schlag G, Morganti-Kossmann MC (1997) Interleukin-8 released into the cerebrospinal fluid after brain injury is associated with blood–brain barrier dysfunction and nerve growth factor production. J Cereb Blood Flow Metab 17:280–289
Martin-Ancel A, Garcia A, Pascual D (1997) Interleukin-6 in the cerebrospinal fluid after perinatal asphyxia is related to early and late neurological manifestations. Pediatrics 100:789–794
Maruo N, Morita I, Shirao M, Murota SI (1992) IL-6 increases endothelial permeability in vitro. Endocrinology 131:710–714
Mathiensen T, Andersson B, Loftenius A, von Holst H (1993) Increased interleukin-6 levels in cerebrospinal fluid following subarachnoid hemorrhage. J Neurosurg 78:562–567
Matsumoto T, Ikeda K, Mukaida N, Harada A, Matsumoto Y, Yamashita J, Matsushima K (1997) Prevention of cerebral edema and infarct in cerebral reperfusion injury by an antibody to interleukin-8. Lab Invest 77:119–125
McClain C, Cohen D, Phillips R, Ott L, Young B (1991) Increased plasma and ventricular fluid interleukin-6 levels in patients with head injury. J Lab Clin Med 118:225–231
Mustafa MM, Lebel MH, Ramilo O, Olsen KD, Reisch JS, Beutler B, McCracken GH Jr (1989) Correlation of interleukin-1β and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis. J Pediatr 115:208–213
Ohtsuki T, Ruetzler CA, Tasaki K, Hallenbeck JM (1996) Interleukin-1 mediates induction of tolerance to global ischemia in gerbil hippocampal CA1 neurons. J Cereb Blood Flow Metab 16:1137–1142
Oygur N, Sonmez O, Saka O, Yegin O (1998) Predictive values of plasma and cerebrospinal fluid TNFα and interleukin 1β concentrations on outcome of full term infants with hypoxic ischemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 79:F190–F193
Pettila V, Hynninen M, Takkunen O, Kuusela P, Valtonen M (2002) Predictive value of procalcitonin and interleukin 6 in critically ill patients with suspected sepsis. Intensive Care Med 21:94–99
Rothwell NJ, Luheshi GN (2000) Interleukin 1 in the brain: biology, pathology and therapeutic target. Trends Neurosci 23:618–625
Satoh T, Nakamura S, Taga T, Matsuda T, Hirano T, Kishimoto T, Kaziro Y (1988) Induction of neuronal differentiation in PC12 cells by B-cell stimulatory factor 2/interleukin-6. Mol Cell Biol 8:3546–3549
Savman K, Blennow M, Gustafson K, Tarkowski E, Hagberg H (1998) Cytokine response in cerebrospinal fluid after birth asphyxia. Pediatr Res 43:746–756
Seekamp A, van Griensven M, Lehmann U, Molituris U, Hildebrandt F, Pohlemann T (2002) Serum IL-6, IL-8 and IL-10 levels in multiple trauma compared to traumatic brain injury and combined trauma. Eur J Trauma 28:183–189
Shalak LF, Laptook AR, Jafri HS, Ramilo O, Perlman JM (2002) Clinical chorioamnionitis, elevated cytokines, and brain injury in term infants. Pediatrics 110:673–680
Sharples PM, Storey A, Aynsley-Green A, Eyre JA (1990) Avoidable factors contributing to death of children with head injury. Br Med J 300:87–91
Sherwood ER, Prough DS (2000) Interleukin-8, neuroinflammation, and secondary brain injury. Crit Care Med 28:1221–1222
Sthael PF, Kossman T, Joller H, Trentz O, Morganti-Kossmann MC (1998) Increased interleukin-12 levels in human cerebrospinal fluid following severe head trauma. Neurosci Lett 249:123–126
Strecker W, Gebhard F, Rager J (2002) Interleukin-6—an early marker of chest trauma. Eur J Trauma 28:75–84
Taupin V, Toulmond S, Serrano A, Benavides J, Zavala F (1993) Increase in IL-6, IL-1 and TNF levels in rat brain following traumatic lesion. Influence of pre- and post-traumatic treatment with Ro5 4864, a peripheral-type (p-site) benzodiazepine ligand. J Neuroimmunol 42:177–186
Whalen MJ, Carlos TM, Clark RS, Marion DW, DeKosky ST, Heineman S, Schiding JK, Memarzadeh F, Kochanek PM (1997) The effect of brain temperature on acute inflammation after traumatic brain injury in rats. J Neurotrauma 14:561–572
Whalen MJ, Carlos TM, Kochanek PM, Wisniewski SR, Bell MJ, Clark RS, DeKosky ST, Marion DW, Adelson PD (2000) Interleukin-8 is increased in cerebrospinal fluid of children with severe head injury. Crit Care Med 28:929–934
Woodroofe MN, Sarna GS, Wadhwa M, Hayes GM, Loughlin AJ, Tinker A, Cuzner ML (1991) Detection of interleukin-1 and interleukin-6 in adult rat brain, following mechanical injury, by in vivo microdialysis: evidence of the role for microglia in cytokine. J Neuroimmunol 33:227–236
Yakovlev AG, Faden AI (1995) Molecular biology of CNS injury. J Neurotrauma 12:767–777
Yamasaki Y, Suzuki T, Yamaya H, Matassumi I, Onodera H, Kogure K (1992) Possible involvement of interleukin-1 in ischemic brain edema formation. Neuroscience 142:45–47
Yamasaki Y, Matsuo Y, Matsuura N, Onodera H, Itoyama Y, Kogure K (1995) Transient increase of cytokine-induced neutrophil chemoattractant, a member of the interleukin-8 family, in ischemic brain areas after focal ischemia in rats. Stroke 26:318–322
Yamasaki Y, Matsuo Y, Zagorski J, Matsuura N, Onodera H, Itoyama Y, Kogure K (1997) New therapeutic possibility of blocking cytokine-induced neutrophil chemoattractant on transient ischemic brain damage in rats. Brain Res 759:103–111
Yan HQ, Banos MA, Herregodts P, Hooghe P, Hooghe-Peters EL (1992) Expression of interleukin IL-1 and IL-6 and their respective receptors in the normal rat and after injury. Eur J Immunol 22:2963–2974
Yatsiv I, Morganti-Kossmann MC, Perez D, Dinarello CA, Novick D, Rubinstein M, Otto VI, Rancan M, Kossmann T, Redaelli CA, Trentz O, Shohami E, Stahel PF (2002) Elevated intracranial IL-18 in humans and mice after traumatic brain injury and evidence of neuroprotective effects of IL-18-binding protein after experimental closed head injury. J Cereb Blood Flow Metab 22:971–978
Yoshidda S, Minakawa T, Takai N, Tanaka R (1989) Effects of cytokines on cultured microvascular endothelial cells derived from gerbil brain. Neurosurgery 25:373–377
Zhang Z, Chopp M, Goussev A, Powers C (1998) Cerebral vessels express interleukin 1β after focal cerebral ischemia. Brain Res 784:210–217
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A commentary on this paper is available at http://dx.doi.org/10.1007/s00381-004-1033-0
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Chiaretti, A., Genovese, O., Aloe, L. et al. Interleukin 1β and interleukin 6 relationship with paediatric head trauma severity and outcome. Childs Nerv Syst 21, 185–193 (2005). https://doi.org/10.1007/s00381-004-1032-1
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DOI: https://doi.org/10.1007/s00381-004-1032-1