Analysis of Immune Mediator Production Following Traumatic Brain Injury

  • T. Kossmann
  • V. H. J. Hans
  • P. M. Lenzlinger
  • E. Csuka
  • P. F. Stahel
  • O. Trentz
  • M. C. Morganti-Kossmann
Conference paper


Patients with severe head injury still carry a high risk of mortality and morbidity despite progress in clinical management (Frankowski et al. 1985; Alberico et al. 1987). Major causes of mortality in these patients are untreatable elevated intracranial pressure (ICP) in the early phase and septic-infectious complications during the later phase (Shackford et al. 1989). The importance of inflammatory events following head trauma even in the absence of systemic injuries has been recognized. Within a short period of time after hospitalization these patients show a depressed T-cell function, an anergy to delayed-type hypersensitivity skin testing, a decrease in the expression of interleukin-2 receptors on T-cells and, furthermore, a diminished in vitro interleukin-2 and γ-interferon production of T-cells as well as suppressed cell cytotoxicity (Quattrocchi et al. 1991; Hoyt et al. 1990). However, the depression of the peripheral immune system may be of a secondary nature and may be regulated by immunological events initiated as a result of the traumatic injury within the brain. In particular cytokines produced and released in the central nervous system (CNS) may play important roles in the pathophysiological events following brain trauma.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aarden LA, DeGroot EF, Schaap OL, Lansdorp PM (1987) Production of hybridoma growth factor by human monocytes. Eur J Immunol 17:1411–1416PubMedCrossRefGoogle Scholar
  2. Aderka D, Le J, Vilcek J (1989) IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells and in mice. J Immunol 143:3517–3523PubMedGoogle Scholar
  3. Akira S, Kishimoto T (1992) IL-6 and NF-IL6 in acute-phase response and viral infection. Immunol Rev 127:25–50PubMedCrossRefGoogle Scholar
  4. Alberico AM, Ward JD, Choi SC, Marmarou A, Young HF (1987) Outcome after severe head injury. Relationship to mass lesions, diffuse injury, and ICP course in pediatric and adult patients. J Neurosurg 67:648–656PubMedCrossRefGoogle Scholar
  5. Aloisi F, Care A, Borsellino G, Gallo P, Rosa S, Bassani A, Cabibbo A, Testa U, Levi G, Peschle C (1992) Production of hemolymphopoietic cytokines (IL-6, IL-8, colony stimulating factors) by normal human astrocytes in response to IL-1β and tumor necrosis factor-α. J Immunol 149:2358–2366PubMedGoogle Scholar
  6. Apfel SC, Lipton RB, Arezzo JC, Kessler JA (1991) Nerve growth factor prevents toxic neuropathy in mice. Ann Neurol 29:87–90PubMedCrossRefGoogle Scholar
  7. Araujo DM, Cotman CW (1993) Trophic effects of interleukin-4, -7 and -8 on hippocampal neuronal cultures: potential involvement of glial derived factors. Brain Res 600:49–55PubMedCrossRefGoogle Scholar
  8. Awatsuji H, Furukawa Y, Hirota M, Murakami Y, Nii S, Furukawa S, Hayashi K (1993) Interleukin-4 and -5 as modulators of nerve growth factor synthesis/secretion in astrocytes. J Neurosci Res 34:539–545PubMedCrossRefGoogle Scholar
  9. Baggiolini M, Walz A, Kunkel SL (1989) Neutrophil-activating peptide-1/interleukin-8, a novel cytokine that activates neutrophils. J Clin Invest 84:1045–1049PubMedCentralPubMedCrossRefGoogle Scholar
  10. Baggiolini M, Dewald B, Moser B (1992) Interleukin-8 and related chemotactic cytokines-CXC and CC chemokines. Adv Immunol 55:97–178CrossRefGoogle Scholar
  11. Banati RB, Gehrmann J, Schubert P, Kreutzberg GW (1993) Cytotoxicity of microglia. Glia 7:111–118PubMedCrossRefGoogle Scholar
  12. Banks WA, Ortiz L, Plotkin SR, Kastin AJ (1991) Human interleukin (IL) la, murine IL-1α and murine IL-1β are transported from blood to brain in the mouse by a shared saturable mechanism. J Pharmacol Exp Ther 259:988–996PubMedGoogle Scholar
  13. Banks WA, Kastin AJ, Broadwell RD (1995) Passage of cytokines across the blood-brain barrier. Neuroimmunomodulation 2:241–248PubMedCrossRefGoogle Scholar
  14. Baumann H, Gauldie J (1994) The acute phase response. Immunol Today 15:74–80PubMedCrossRefGoogle Scholar
  15. Bazzoni F, Cassatella MA, Rossi F, Ceska M, Dewals B, Baggiolini M (1991) Phagocytosing neutrophils produce and release high amounts of neutrophil-activating peptide 1/interleukin-8. J Exp Med 173:771–774PubMedCrossRefGoogle Scholar
  16. Benveniste E (1995) The role of cytokines in multiple sclerosis/autoimmune encephalitis and other neurological disorders. In: Agarwal B, Puri R (eds) Human cytokines, their role in research and therapy. Blackwell, Boston/MA, pp 195–216Google Scholar
  17. Bodmer S, Strommer K, Frei K, Siepl C, de Tribolet N, Heid I, Fontana A (1989) Immunosup-pression and transforming growth factor-β in glioblastoma. J Immunol 143: 3222–3229PubMedGoogle Scholar
  18. Bowes MP, Zivin JA, Rothlein R (1993) Monoclonal antibody to the ICAM-1 adhesion site reduces neurological damage in a rabbit cerebral embolism stroke model. Exp Neurol 119:215–219PubMedCrossRefGoogle Scholar
  19. Carman-Krzan M, Vige X, Wise BC (1991) Regulation by Interleukin-1 of nerve growth factor mRNA expression in rat primary astroglial cultures. J Neurochem 56:636–643PubMedCrossRefGoogle Scholar
  20. Castell JV, Geiger T, Gross V, Andus T, Walter E, Hirano T, Kishimoto T, Heinrich PC (1988) Plasma clearance, organ distribution and target cells of interleukin-6/hepatocyte- stimulating factor in the rat. Eur J Biochem 177:357–361PubMedCrossRefGoogle Scholar
  21. Castell JV, Gómez-Lechón MJ, David M, Andus T, Geiger T, Trullenque R, Fabra R, Heinrich PC (1989) Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes. FEBS Lett 242:237–239PubMedCrossRefGoogle Scholar
  22. Chan PH, Schmidley JW, Fishman RA, Longar SM (1984) Brain injury, edema, and vascular permeability changes induced by oxygen derived free redicals. Neurology (NY) 34:315–320CrossRefGoogle Scholar
  23. Clark JM (1974) Distribution of microglial clusters in the brain after head injury. J Neurol Neurosurg Psychiatry 37:463–474PubMedCrossRefGoogle Scholar
  24. Constam DB, Philipp J, Malipiero UV, ten Dijke P, Schachner M, Fontana A (1992) Differential expression of transforming growth factor- β1, -β2 and - β3 by glioblastoma cells, astrocytes and microglia. J Immunol 148:1404–1410PubMedGoogle Scholar
  25. Cortez SC, Mcintosh TK, Noble LJ (1989) Experimental fluid percussion brain injury: vascular disruption and neuronal and glial alterations. Brain Res 482:271–282PubMedCrossRefGoogle Scholar
  26. Cross EM, Chaffin WW (1982) Use of the binomial theorem in interpreting results of multiple tests of significance. Educ Psychol Measurem 42:25–34CrossRefGoogle Scholar
  27. Da Cuhna A, Jefferson JA, Jackson RW, Vitovic L (1993) Glial specific mechanisms of TGF- β1 induction by IL-1 in cerebral cortex. J Neuroimmunol 42:71–86CrossRefGoogle Scholar
  28. Dinarello CA (1991) Interleukin-1 and Interleukin-1 antagonism. Blood 77:1627–1652PubMedGoogle Scholar
  29. Dixon CE, Lighthall JW, Anderson TE (1988) Physiologic, histopathologic, and cineradiographic characterization of a new fluid-percussion model of experimental brain injury in the rat. J Neurotrauma 5:91–104PubMedCrossRefGoogle Scholar
  30. Dubravec DB, Spriggs DR, Mannick JA, Rodrick ML (1990) Circulating human peripheral blood granulocytes synthesize and secrete tumor necrosis factor a. Proc Natl Acad Sci USA 87:6758–6761PubMedCrossRefGoogle Scholar
  31. Eddieston M, Mucke L (1992) Molecular profile of reactive astrocytes-implication for their role in neurologic disease. Neuroscience 54:15–36CrossRefGoogle Scholar
  32. Fabry Z, Raine CS, Hart MN (1994) Nervous tissue as an immune compartment: the dialect of the immune response in the CNS. Immunol Today 15:218–224PubMedCrossRefGoogle Scholar
  33. Feldman Z, Contant CF, Pahwa R, Goodman JC, Robertson CS, Narayan RK, Grossman RG (1993) The relationship between hormonal mediators and systemic hypermetabolism after severe head injury. J Trauma 34:806–816PubMedCrossRefGoogle Scholar
  34. Foda MA, Marmarou A (1994) A new model of diffuse brain injury in rats. II. Morphological characterization. J Neurosurg 80:301–313PubMedCrossRefGoogle Scholar
  35. Frankowski RF, Annegers JF, Whitman S (1985) The descriptive epidemiology of head trauma in US. In: Becker DP, Povlishock JT (eds) Central nervous system trauma. Status report. National Institutes of Health, Bethesda, pp 89–122Google Scholar
  36. Frei K, Leist TP, Meager A, Gallo P, Leppert D, Zinkernagel RM, Fontana A (1988) Production of B cell stimulatory factor-2 and interferon-γ in the central nervous system during viral meningitis and encephalitis. J Exp Med 168:449–453PubMedCrossRefGoogle Scholar
  37. Frei K, Malipiero UV, Leist TP, Zinkernagel RM, Schwab ME, Fontana A (1989) On the cellular source and function of interleukin 6 produced in the central nervous system in viral diseases. Eur J Immunol 19:689–694PubMedCrossRefGoogle Scholar
  38. Frei K, Nadal D, Fontana A (1990) Intracerebral synthesis of tumor necrosis factor-α and interleukin-6 in infectious meningitis. Ann N Y Acad Sci 594:326–335PubMedCrossRefGoogle Scholar
  39. Frei K, Piani D, Pfister HW, Fontana A (1993) Immune-mediated injury in bacterial meningitis. Int Rev Exp Pathol 34:183–192PubMedCrossRefGoogle Scholar
  40. Frohman EM, Frohman TC, Dustin ML, Vayuvegula B, Choi B, Gupta A, van den Noort S, Gupta S (1989) The induction of intracellular adhesion molecule 1 (ICAM-1) expression on human fetal astrocytes by interferon-γ, tumor necrosis factor-α, lymphotoxin and Interleukin-1: relevance to intracerebral antigen presentation. J Neuroimmunol 23:117–124PubMedCrossRefGoogle Scholar
  41. Furukawa Y, Tomioka N, Sato W, Satoyoshi E, Hayashi K, Furukawa S (1989) Catecholamines increase nerve growth factor mRNA content in both mouse astroglial cells and fibroblast cells. FEBS Lett 247:395–402CrossRefGoogle Scholar
  42. Gadient RA, Cron KC, Otten U (1990) Interleukin-1β and tumor necrosis factor-a synergistically stimulate nerve growth factor (NGF) release from cultured rat astrocytes. Neurosci Lett 117:335–340PubMedCrossRefGoogle Scholar
  43. Gallo P, Frei K, Rordorf C, Lazdins J, Tavolato B, Fontana A (1989) Human immunodeficiency virus type I (HIV-1) infection of the central nervous system: an evaluation of cytokines in cerebrospinal fluid. J Neuroimmunol 23:109–116PubMedCrossRefGoogle Scholar
  44. Gennarelli TA, Spielman GM, Langfitt TW, Gildenberg PL, Harrington T, Jane JA, Marshall LF, Miller JD, Pitts LH (1982) Influence of the type of intracranial lesion on outcome from severe head injury. J Neurosurg 56:26–32PubMedCrossRefGoogle Scholar
  45. Giulian D, Lachman LB (1985) Interleukin-1 stimulation of astroglial proliferation after brain injury. Science 228:4707–4717CrossRefGoogle Scholar
  46. Giulian D, Ingeman JE, George JK, Noponen M (1989) The role of mononuclear phagocytes in wound healing after traumatic brain injury to adult mammalian brain. J Neurosci 9:4416–1129PubMedGoogle Scholar
  47. Halstensen A, Ceska M, Brandtzaeg P, Redl H, Naess A, Waage A (1993) Interleukin-8 in serum and cerebrospinal fluid from patients with meningococcal disease. J Infect Dis 167:471–475PubMedCrossRefGoogle Scholar
  48. Hama T, Miymoto 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 104:340–344PubMedCrossRefGoogle Scholar
  49. Handa S (1992) Concentrations of interleukin-Iβ, interleukin-6, interleukin-8 and TNF-a in cerebrospinal fluid from children with septic or aseptic meningitis. Kurume Med J 39:257–265PubMedCrossRefGoogle Scholar
  50. Heumann R, Korshing S, Bandtlow C, Thoenen H (1987) Changes of nerve growth factor synthesis in non-neuronal cells in response to sciatic nerve transection. J Cell Biol 104:1623–1631PubMedCrossRefGoogle Scholar
  51. Hirano T, Taga T, Nakano N, Yasukawa K, Kashiwamura S, Shimizu K, Nakajima K, Pyun KH, Kishimoto T (1985) Purification to homogeneity and characterization of human B-cell differentiation factor (BCDF or BSFp-2). Proc Natl Acad Sci USA 84:5490–5494CrossRefGoogle Scholar
  52. Hosford D, Braquet P (1989) Potential role for platelet-activating factor and tumor necrosis factor in the immune impairments in shock and trauma. In: Faist E, Ninnemann J, Green D (eds) Immune consequences of trauma, shock and sepsis. Springer, Berlin, Heidelberg New York, pp 311–321CrossRefGoogle Scholar
  53. Hoyt DB, Ozkan N, Hansbrough JF, Marshall L, van Berkum-Clark M (1990) Head injury: an immunologic deficit in T-cell activation. J Trauma 30:759–767PubMedCrossRefGoogle Scholar
  54. Ishibashi T, Kimura H, Shikama Y, Uchida T, Kariyone S, Hirano T, Kishimoto T, Takatsuki F, Akiyama Y (1989) Interleukin-6 is a potent thrombopoietic factor in vivo in mice. Blood 74:1241–1244PubMedGoogle Scholar
  55. Jennett B, Bond M (1975) Assessment of outcome after severe brain damage. Lancet 1:480–484PubMedCrossRefGoogle Scholar
  56. Kim KS, Wass CA, Cross AS, Opal SM (1992) Modulaton of blood-brain barrier permeability by tumor necrosis factor and antibody to tumor necrosis factor in the rat. Lymphokine Cytokine Res 11:293–298PubMedGoogle Scholar
  57. Kitamura T, Ogorochi T, Miyajima A (1994) Multimeric cytokine receptors. Trends Endocrinol Metab 5:8–14PubMedCrossRefGoogle Scholar
  58. Kossmann T, Hans V, Imhof HG, Stocker R, Grob P, Trentz O, Morganti-Kossmann MC (1995) Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries. Shock 4:311–317PubMedCrossRefGoogle Scholar
  59. 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 713:143–152PubMedCrossRefGoogle Scholar
  60. 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 (in press)Google Scholar
  61. Kromer LF (1986) Nerve growth factor treatment after brain injury prevents neuronal death. Science 235:214–216CrossRefGoogle Scholar
  62. Kuruvilla AP, Shah R, Hochwald GM, Liggitt HD, Palladino MA, Thorbecke GJ (1991) Protective effect of transforming growth factor β1 on experimental autoimmune diseases in mice. Proc Natl Acad Sci USA 88:2918–2921PubMedCrossRefGoogle Scholar
  63. Kushner I, Mackiewicz A (1987) Acute phase proteins as disease markers. Dis Markers 5:1–11PubMedGoogle Scholar
  64. Lacy M, Jones J, Whittemore SR, Haviland DL, Wetsel RA, Barnum SR (1995) Expression of the receptors for the C5a anaphylatoxin, interleukin-8 and FMLP by human astrocytes and microglia. J Neuroimmunol 61:71–78PubMedCrossRefGoogle Scholar
  65. Leppert D, Frei K, Gallo P, Yasargil MG, Hess K, Baumgartner G, Fontana A (1989) Brain tumors: detection of B-cell stimulatory factor-2/interleukin-6 in the absence of oligoclonal bands of immunoglobulins. J Neuroimmunol 24:259–264PubMedCrossRefGoogle Scholar
  66. Levi-Montalcini R, Angeletti PU (1968) Nerve growth factor. Physiol Rev 48:534–569PubMedGoogle Scholar
  67. Lindholm D, Heumann R, Meyer M, Thoenen H (1987) Interleukin-1 regulates synthesis of nerve growth factor in non neuronal cells of rat sciatic nerve. Nature 330:658–659PubMedCrossRefGoogle Scholar
  68. Lindholm D, Hengerer B, Zafra F, Thoenen H (1990) Transforming growth factor-β1 stimulates the expression of nerve growth factor in the rat CNS. Dev Neurosci 1:9–12Google Scholar
  69. Lindholm D, Castren E, Kiefer R, Zafra F, Thoenen H (1992) Transforming growth factor-β1 in the rat brain: increase after injury and inhibition of astrocyte proliferation. J Cell Biol 117:395–400PubMedCrossRefGoogle Scholar
  70. Lindsay RM (1979) Adult rat brain astrocytes support survival of both NGF-dependent and NGF-insensitive neurons. Nature 282:80–82PubMedCrossRefGoogle Scholar
  71. Logan A, Frautschy SA, Gonzalez AM, Sporn MB, Baird A (1992) Enhanced expression of transforming growth factor-β1 in the rat brain after localized cerebral injury. Brain Res 587:216–225PubMedCrossRefGoogle Scholar
  72. Lotem J, Shabo Y, Sachs L (1989) Regulation of megakaryocyte development by interleukin-6. Blood 74:1545–1551PubMedGoogle Scholar
  73. Maimone D, Gregory S, Arnason BGW, Reder AT (1991) Cytokine levels in the cerebrospinal fluid and serum of patients with multiple sclerosis. J Neuroimmunol 32:67–74PubMedCrossRefGoogle Scholar
  74. Marmarou A, Foda MA, van den Brink W, Campbell J, Kita H, Demetriadou K (1994) A new model of diffuse brain injury in rats. I. Pathophysiology and biomechanics. J Neurosurg 80:291–300PubMedCrossRefGoogle Scholar
  75. Marshall LF, Marshall SB, Klauber MR, Clarck MVB, Eisenberg HM, Jane JA, Luerssen TG, Marmarou A, Foulkes M (1991) A new classification of head injury based on computerized tomography. J Neurosurg 75:S14–S20Google Scholar
  76. Martich GD, Danner RL, Ceska M, Suffredini AF (1991) Detection of interleukin-8 and tumor necrosis factor in normal humans after intravenous endotoxin: the effect of antiinflammatory agents. J Exp Med 173:1021–1024PubMedCrossRefGoogle Scholar
  77. Marucha PT, Zeff RA, Kreutzer DL (1990) Cytokine regulation of IL-1β gene expression in the human polymorphonuclear leukocyte. J Immunol 145:2932–2937PubMedGoogle Scholar
  78. Mastroianni CM, Paoletti F, Rivosecchi RM, Lancella L, Ticca F, Vullo V, Delia S (1994) Cerebrospinal fluid interleukin-8 in children with purulent bacterial and tuberculous meningitis. Pediatr Infect Dis J 13:1008–1010PubMedCrossRefGoogle Scholar
  79. Mathiesen T, Andersson B, Loftenius A, von Holst H (1993) Increased interleukin-6 levels in cerebrospinal fluid following subarachnoid hemorrhage. J Neurosurg 78:562–567PubMedCrossRefGoogle Scholar
  80. McClain CJ, Cohen D, Ott L, Dinarello C, Young B (1987) Ventricular fluid Interleukin-1 activity in patients with head injury. J Lab Clin Med 110:48–54PubMedGoogle Scholar
  81. McClain C, Cohen D, Phillips R, Ott L, Young AB (1991) Increased plasma and ventricular fluid interleukin-6 levels in patients with head injury. J Lab Clin Med 118:226–231Google Scholar
  82. Morganti MC, Taylor J, Pesheva P, Schachner M (1990) Oligodendrocyte-derived Jl-160/180 extracellular matrix glycoproteins are adhesive or repulsive depending on the partner cell type and time of interaction. Exp Neurol 109:98–110PubMedCrossRefGoogle Scholar
  83. Morganti-Kossmann MC, Kossmann T (1995) The immunology of brain injury. In: Rothwell NJ (ed) Immune responses in the nervous system. Bios Scientific, Oxford, pp 159–187Google Scholar
  84. Morganti-Kossmann MC, Kossmann T, Wahl SM (1992a) Cytokines and neuropathology. Trends Pharmacol Sci 13:286–291PubMedCrossRefGoogle Scholar
  85. Morganti-Kossmann MC, Kossmann T, Brandes ME, Mergenhagen SE, Wahl SM (1992b) Autocrine and paracrine regulation of astrocyte function by transforming growth factor-β. J Neuroimmunol 39:163–174PubMedCrossRefGoogle Scholar
  86. Morita M, Kasahara T, Mukaida N, Matsushima K, Nagashima T, Nishizawa M, Yoshida M (1993) Induction and regulation of interleukin-8 and MCAF production in human brain tumor cell lines and brain tumor tissues. Eur Cytokine Netw 4:351–358PubMedGoogle Scholar
  87. Mosmann T (1983) Rapid cholorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assay. J Immunol Methods 65:55–63PubMedCrossRefGoogle Scholar
  88. Mukaida N, Matsushima K (1992) Regulation of interleukin-8 production and the characteristics of the receptors for interleukin-8. Cytokines 4:41–53PubMedGoogle Scholar
  89. Nieto-Sampedro M, Berman MA (1987) Interleukin-1 like activity in rat brain: sources, targets and effects of injury. J Neurosci Res 17:214–219PubMedCrossRefGoogle Scholar
  90. Nieto-Sampedro M, Lewis ER, Cotman CW, Manthorpe M, Skaper SD, Barbin G, Longo FM, Varon S (1982) Brain injury causes a time-dependent increase in neuronotrophic activity at the lesion site. Science 217:860–861PubMedCrossRefGoogle Scholar
  91. Nijsten MWN, Hack CE, Helle M, ten Duis HJ, Klasen HJ, Aarden LA (1991) Interleukin-6 and its relation to the humoral immune response and clinical parameters in burned patients. Surgery 109:761–767PubMedGoogle Scholar
  92. Nitta T, Allegretta M, Okumura K, Sato K, Steinman L (1992) Neoplastic and reactive human astrocytes express interleukin-8 gene. Neurosurg Rev 15:203–207PubMedCrossRefGoogle Scholar
  93. Okada M, Sakaguchi N, Yoshimura N, Hara H, Shimizu K, Yoshida N, Yoshizaki K, Kishimoto S, Yamamura Y, Kishimoto T (1983) B cell growth factors and B cell differentiation factor from human T hybridomas: two distinct kinds of B cell growth factors and their synergism in B cell proliferation. J Exp Med 157:583–590PubMedCrossRefGoogle Scholar
  94. Pasinetti GM, Nichols NR, Tocco G, Morgan T, Laping N, Finch CE (1993) Transforming growth factor β1 and fibronectin messenger RNA in rat brain: responses to injury and cell type localization. Neuroscience 54:893–907PubMedCrossRefGoogle Scholar
  95. Patterson SL, Grady MS, Bothwell M (1993) Nerve growth factor and fibroblast growth factor-like neurotrophic activity in cerebrospinal fluid of brain injured human patients. Brain Res 605:43–49PubMedCrossRefGoogle Scholar
  96. Prehn JHM, Peruche B, Unsicker K, Krieglstein J (1993) Isoform specific effects of transforming growth factor-β on degeneration of primary neuronal cultures induced by cytotoxic hypoxia or glutamate. J Neurochem 60:1665–1672PubMedCrossRefGoogle Scholar
  97. Quattrocchi KB, Frank EH, Miller CH, Amin A, Issel BW, Wagner FC Jr (1991) Impairment of helper T-cell function and lymphokine-activated killer cytotoxicity following severe head injury. J Neurosurg 75:766–773PubMedCrossRefGoogle Scholar
  98. Racke MK, Jalbut SD, Cannella B, Albert PS, Raine CS, McFarlin DE (1991) Prevention and treatment of chronic relapsing experimental allergic encephalomyelitis by transforming growth factor-β1. J Immunol 146:3012–3017PubMedGoogle Scholar
  99. Reiber H, Felgenhauer K (1987) Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the humoral immune response within the central nervous system. Clin Chim Acta 163:319–328PubMedCrossRefGoogle Scholar
  100. Satoh T, Nakamura S, Taga T, Matsuda T, Hirano, Kishimoto T, Kairo Y (1988) Induction of neuronal differentiation in PC 12 cells by B cell stimulatory factor-2/interleukin-6. Mol Cell Biol 8:3546–3549PubMedCentralPubMedGoogle Scholar
  101. Seki T, Joh K, Oh-ishi T (1993) Augmented production of interleukin-8 in cerebrospinal fluid in bacterial meningitis. Immunology 80:333–335PubMedGoogle Scholar
  102. Selmaj KW, Farooq M, Norton WT, Raine CS, Brosnan CF (1990) Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor. J Immunol 144:129–135PubMedGoogle Scholar
  103. Selmaj KW, Raine CS, Farooq M, Norton WT, Brosnan CF (1991) Cytokine cytotoxicity against oligodendrocytes apoptosis induced by lymphotoxin. J Immunol 147: 1522–1529PubMedGoogle Scholar
  104. Shackford SR, Mackersie RC, Davis JW, Wolf PL, Hoyt DB (1989) Epidemiology and pathology of traumatic deaths occurring at a level I trauma center in a regionalized system: the importance of secondary brain injury. J Trauma 29:1392–1397PubMedCrossRefGoogle Scholar
  105. Shiga Y, Onodera H, Kogure K, Yamasaki Y, Yashima Y, Syozuhara H, Sendo F (1991) Neutrophil as a mediator of ischemic edema formation in the brain. Neurosci Lett 125:110–112PubMedCrossRefGoogle Scholar
  106. Spranger M, Lindholm D, Bandtlow C, Heumann R, Gnahn H, Naeher-Noe M, Thoenen H (1990) Regulation of nerve growth factor (NGF) synthesis in the rat central nervous system: comparison between the effects of Interleukin-1 and various growth factors in astrocyte cultures and in vivo. Eur J Neurosci 2:69–76PubMedCrossRefGoogle Scholar
  107. Stocker R, Bernays R, Kossmann T, Imhof H-G (1995) Monitoring and treatment of acute head injury. In: Goris RJA, Trentz O (eds) The integrated approach to trauma care. Springer, Berlin Heidelberg New York, pp 197–210Google Scholar
  108. Tada M, Suzuki K, Yamakawa Y, Sawamura Y, Sakuma S, Abe H, van Meir E, de Tribolet N (1993) Human glioblastoma cells produce 77 amino acid interleukin-8. J Neuro Oncol 16:25–34CrossRefGoogle Scholar
  109. 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. J Neuroimmunol 42:177–186PubMedCrossRefGoogle Scholar
  110. Teasdale G, Jennett B (1974) Assessment of coma and impaired consciousness. A practical scale. Lancet 2:81–84PubMedCrossRefGoogle Scholar
  111. Terebuh PD, Otterness IG, Strieter RM, Lincoln PM, Danforth JM, Kunkel SL, Chensue SW (1992) Biologic and immunhistochemical analysis of interleukin-6 expression in vivo. Am J Pathol 140:649–657PubMedGoogle Scholar
  112. Van Damme J, De Ley M, van Snick J, Dinarello C, Billiau A (1987) The role of interferon-β1 and the 26kDa protein (interferon-β2) as mediators of the antiviral effect of Interleukin-1 and tumor necrosis factor. J Immunol 139:1867–1872PubMedGoogle Scholar
  113. Van den Brink WA, Marmarou A, Avezaat CJ (1990) Brain oedema in experimental closed head in jury in the rat. Acta Neurochir Suppl (Wien) 51:261–262Google Scholar
  114. Van Meir E, Ceska M, Effenberger F, Walz A, Grouzmann E, Desbaillets I, Frei K, Fontana A, de Tribolet N (1992) Interleukin-8 is produced in neoplastic and infectious diseases of the human central nervous system. Cancer Res 52:4297–4305PubMedGoogle Scholar
  115. Van Snick J (1990) Interleukin-6: an overview. Annu Rev Immunol 8:253–278PubMedCrossRefGoogle Scholar
  116. Wahl SM (1994) Transforming growth factor beta (TGF-β) in inflammation: a cause and a cure. J Clin Immunol 12:61–74CrossRefGoogle Scholar
  117. Wahl SM, Allen JB, McCartney-Francis N, Morganti-Kossmann MC, Kossmann T, Ellingsworth L, Mai UEH, Mergenhagen SE, Orenstein JM (1991) Macrophage- and astrocyte-derived transforming growth factor-β as a mediator of central nervous system dysfunction in acquired immunodeficiency syndrome. J Exp Med 173:981–991PubMedCrossRefGoogle Scholar
  118. Wiessner C, Gehrmann J, Lindholm D, Toepper R, Kreutzberg GW, Hossmann KA (1993) Expression of transforming growth factor-β1 and interleukin-lβ mRNA in rat brain following transient forebrain ischemia. Acta Neuropathol (Berl) 86:439–446CrossRefGoogle Scholar
  119. 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 a role for microglia in cytokine production. J Neuroimmunol 33:227–236PubMedCrossRefGoogle Scholar
  120. Yoshida K, Gage FH (1991) Fibroblast growth factors stimulate nerve growth factor synthesis and secretion by astrocytes. Brain Res 538:118–126PubMedCrossRefGoogle Scholar
  121. Young AB, Ott LG, Beard D, Dempsey RJ, Tibbs PA, McClain CJ (1988) The acute-phase response of the brain-injured patient. J Neurosurg 69:375–380PubMedCrossRefGoogle Scholar
  122. Zhou D, Munster A, Winchurch RA (1991) Pathologie concentrations of interleukin-6 inhibit T cell responses via induction or activation of TGF-β. FASEB J 5:2582–2585PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • T. Kossmann
  • V. H. J. Hans
  • P. M. Lenzlinger
  • E. Csuka
  • P. F. Stahel
  • O. Trentz
  • M. C. Morganti-Kossmann

There are no affiliations available

Personalised recommendations