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The Neuroimmunology of Tumour Necrosis Factor-α

  • Review Article
  • Immunological Basis of Disease
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Summary

Tumour necrosis factor-α (TNFα) is a pleiotropic cytokine involved in the pathogenesis of a number of systemic diseases. Its involvement in neuroimmunology has recently been highlighted.

TNFα is produced in the central nervous system (CNS) by neurons, astrocytes and microglia. It possesses a diverse repertoire of activities within the CNS, ranging from facilitation of antigen presentation by astrocytes to direct toxicity on oligodendrocytes and myelin. Recent studies have found that TNFα may be important in the pathogenesis of bacterial meningitis, cerebral malaria, demyelinating diseases, acquired immunodeficiency syndrome (AIDS) and gliomas. Novel treatment methods are under active investigation, including inhibition of TNFα biosynthesis by agents such as dexamethasone, and the neutralisation of its biological effects with monoclonal antibodies or other experimental drugs.

Since CNS injury may be caused by an overabundant inflammatory response, the blunting of the activity of TNFα, a pivotal mediator in the cytokine cascade, may prove beneficial to the host. Any clinical role for TNFα will be defined by the balance between its beneficial and injurious effects. For instance, a therapeutic role for TNFα in gliomas will be based on the potential to minimise its effects while simultaneously increasing its tumour cytotoxicity.

Better understanding of the interactions of TNFα within the neuroimmunological cytokine network will lead to new treatments for disabling neurological diseases.

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References

  1. Decker T, Lohmann Matthes ML, Karck U, et al. Comparative study of cytotoxicity, tumor necrosis factor, and prostaglandin release after stimulation of rat Kupffer cells, murine Kupffer cells, and murine inflammatory liver macrophages. J Leukoc Biol 1989; 45: 139–46

    PubMed  CAS  Google Scholar 

  2. Beutler B, Brown T. A CAT reporter construct allows ultrasensitive estimation of TNF synthesis, and suggests that the TNF gene has been silenced in non-macrophage cell lines. J Clin Invest 1991; 87: 1336–44

    Article  PubMed  CAS  Google Scholar 

  3. Dubravec DB, Spriggs DR, Mannick JA, et al. Circulating human peripheral blood granulocytes synthesize and secrete tumor necrosis factor-alpha. Proc Natl Acad Sci USA 1990; 87: 6758–61

    Article  PubMed  CAS  Google Scholar 

  4. Chensue SW, Terebuh PD, Remick DG, et al. In vivo biologic and immunohistochemical analysis of interleukin-1 alpha, beta and tumor necrosis factor during experimental endotoxemia: kinetics, Kupffer cell expression, and glucocorticoid effects. Am J Pathol 1991; 138: 395–402

    PubMed  CAS  Google Scholar 

  5. Sharif SF, Hariri RJ, Chang VA, et al. Human astrocyte production of tumour necrosis factor-alpha, interleukin-1B, and interleukin-6 following exposure to lipopolysaccharide endotoxin. Neurol Res 1993; 15: 109–12

    PubMed  CAS  Google Scholar 

  6. Pillai S, Bikle DD, Eessalu TE, et al. Binding and biological effects of tumor necrosis factor alpha on cultured human neonatal foreskin keratinocytes. J Clin Invest 1989; 83: 816–21

    Article  PubMed  CAS  Google Scholar 

  7. Larsen CG, Zachariae CO, Oppenheim JJ, et al. Production of monocyte chemotactic and activating factor (MCAF) by human dermal fibroblasts in response to interleukin 1 or tumor necrosis factor. Biochem Biophys Res Commun 1989; 160: 1403–8

    Article  PubMed  CAS  Google Scholar 

  8. Figueres AP, Raetz CRH. Processing and secretion of TNF-α in endotoxin-treated mono mac 6 cells are dependent on phorbol myristate acetate. J Biol Chem 1992; 267: 23261–8

    Google Scholar 

  9. Nedwin GE, Naylor SL, Sakaguch AY, et al. Human lymphotoxin and TNF α genes: structure, homology and chromosomal localization. Nucleic Acids Res 1985; 13: 6361–73

    Article  PubMed  CAS  Google Scholar 

  10. Smith RA, Baglioni C. The active form of tumor necrosis factor is a trimer. J Biol Chem 1987; 262: 6951–4

    PubMed  CAS  Google Scholar 

  11. Pfizenmaier K, Himmler A, Schütze S, et al. TNF receptors and TNF signal transduction. In: Beutler B, editor. Tumor necrosis factors: the molecules and their emerging role in medicine. New York: Raven Press, 1992: 439–72

    Google Scholar 

  12. Tracey KJ. The acute and chronic pathophysiological effects of TNF: mediation of septic shock and wasting (cachexia). In: Beutler B, editor. Tumor necrosis factors: the molecules and their emerging role in medicine. New York: Raven Press, 1992: 255–73

    Google Scholar 

  13. Breder CD, Saper CB. TNF immunoreactive innervation in the mouse brain [abstract]. Soc Neurosci Abstr 1988; 144: 1280

    Google Scholar 

  14. Chung IY, Benveniste EN. Tumor necrosis factor-α production by astrocytes. J Immunol 1990; 144: 2999–3007

    PubMed  CAS  Google Scholar 

  15. Lieberman AP, Pitha PM, Shin HS, et al. Production of tumor necrosis factor and other cytokines by astrocytes stimulated with lipopolysaccharide or a neurotropic virus. Proc Natl Acad Sci USA 1989; 86: 6348–52

    Article  PubMed  CAS  Google Scholar 

  16. Ricciardi-Castagnoli P, Pirami L, Righi M, et al. Cellular sources and effects of a tumor necrosis factor-α on pituitary cells and in the central nervous system. Ann N Y Acad Sci 1993; 156–67

    Google Scholar 

  17. Sawada M, Kondo N, Suzumura A, et al. Production of tumor necrosis factor-alpha by microglia and astrocytes in culture. Brain Res 1989; 491: 394–7

    Article  PubMed  CAS  Google Scholar 

  18. Ramilo O, Saez-Llorens X, Mertsola J, et al. Tumor necrosis factor α/cachectin and interleukin 1β initiate meningeal inflammation. J Exp Med 1990; 172: 497–507

    Article  PubMed  CAS  Google Scholar 

  19. Saukkonen K, Sande S, Cioffe C, et al. The role of cytokines in the generation of inflammation and tissue damage in experimental gram-positive meningitis. J Exp Med 1990; 171: 439–48

    Article  PubMed  CAS  Google Scholar 

  20. Yamasaki T, Kijuchi H, Moritake K, et al. A morphological and ultrastructural investigation of normal mouse brain tissue after intracerebral injection of tumor necrosis factor. J Neurosurg 1992; 77: 279–87

    Article  PubMed  CAS  Google Scholar 

  21. Tracey KJ, Morgello S, Koplin B, et al. Metabolic effects of cachectin/tumor necrosis factor are modified by site of production: cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominately acute anorexia. J Clin Invest 1990; 86: 2014–24

    Article  PubMed  CAS  Google Scholar 

  22. Bodnar RJ, Pasternak GW, Mann PE, et al. Mediation of anorexia by human recombinant tumor necrosis factor through a peripheral action in the rat. Cancer Res 1989; 49: 6280–4

    PubMed  CAS  Google Scholar 

  23. Plata-Salaman CR, Oomura Y, Kai Y. TNF and IL-1β: suppression of food intake by direct action in the central nervous system. Brain Res 1988; 448: 106–14

    Article  PubMed  CAS  Google Scholar 

  24. Barna BP, Estes ML, Jacobs BS, et al. Human astrocytes proliferate in response to tumor necrosis factor alpha. J Neuroimmunol 1990; 30: 239–43

    Article  PubMed  CAS  Google Scholar 

  25. Selmaj KW, Farooq M, Norton WT, et al. Proliferation of astrocytes in vitro in response to cytokines: a primary role for tumor necrosis factor. J Immunol 1990; 144: 129–35

    PubMed  CAS  Google Scholar 

  26. Robbins DS, Shirazi Y, Drysdale B, et al. Production of cytotoxin factor for oligodendrocytes by stimulating astrocytes. Immunology 1987; 139: 2593–7

    CAS  Google Scholar 

  27. Selmaj KW, Raine CS. TNF mediates myelin and oligodendrocyte damage in vitro. Ann Neurol 1988; 29: 339–46

    Article  Google Scholar 

  28. Terada LS, Willingham IR, Guidot DM, et al. Tungsten treatment prevents tumor necrosis factor-induced injury of brain endothelial cells. Inflammation 1992; 16: 13–9

    Article  PubMed  CAS  Google Scholar 

  29. Lavi E, Suzumura A, Murasko DM, et al. TNF induces expression of MHC Class I antigens on mouse astrocytes. J Neuroimmunol 1988; 18: 245–53

    Article  PubMed  CAS  Google Scholar 

  30. Massa PT, Schimpl A, Wecker E, et al. Tumor necrosis factor amplifies measles virus-mediated Ia induction on astrocytes. Proc Natl Acad Sci USA 1987; 84: 7242–5

    Article  PubMed  CAS  Google Scholar 

  31. Mauerhoff T, Pujol-Borell R, Mirakian R, et al. Differential expression and regulation of major histocompatibility complex (MHC) products in neural and glial cells of the human fetal brain. J Immunol 1988; 18: 271–89

    CAS  Google Scholar 

  32. Benveniste EN, Sparacio SM, Bethea JR. Tumor necrosis factor-α enhances interferon-gamma-mediated class II antigen expression on astrocytes. J Neuroimmunol 1989; 25: 209–19

    Article  PubMed  CAS  Google Scholar 

  33. Cannella B, Raine CS. Cytokines up-regulate Ia expression in organotypic cultures of central nervous system tissue. J Neuroimmunol 1989; 24: 239–48

    Article  PubMed  CAS  Google Scholar 

  34. Tanaka M, McCarron RM. The inhibitory effect of tumor necrosis factor and interleukin-1 on Ia induction by interferongamma on endothelial cells from murine central nervous system microvessels. J Immunol 1990; 27: 209–15

    CAS  Google Scholar 

  35. Frohman EM, Frohman TC, Dustin ML, et al. The induction of intercellular adhesion molecule 1 (ICAM-1) expression on human fetal astrocytes by interferon-gamma, tumor necrosis factor alpha, lymphotoxin, and interleukin-1: relevance to intracerebral antigen presentation. J Neuroimmunol 1989; 23: 117–24

    Article  PubMed  CAS  Google Scholar 

  36. Satoh JI, Kastrukoff LF, Kim SU. Cytokine-induced expression of intercellular adhesion molecule-1 (ICAM-1) in cultured human oligodendrocytes and astrocytes. J Neuropathol Exp Neurol 1991; 50: 215–24

    Article  PubMed  CAS  Google Scholar 

  37. Hurwitz AA, Lyman WD, Guida MP, et al. TNF alpha induces adhesion molecule expression on human fetal astrocytes. J Exp Med 1992; 176: 1631–6

    Article  PubMed  CAS  Google Scholar 

  38. Seibre G, Hery C, Peudenier S, et al. Adhesion proteins on human microglial cells and modulation of their expression of IL-1α and TNFα. Res Virol 1993; 144: 47–52

    Article  Google Scholar 

  39. Tweardy DJ, Glazer EW, Mott PL, et al. Modulation by tumor necrosis factor-α of human astroglial cell production by granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). J Neuroimmunol 1991; 32: 269–78

    Article  PubMed  CAS  Google Scholar 

  40. Frei K, Malipiero UV, Zinkernagel RM, et al. On the cellular source and function of interleukin 6 produced in the central nervous system in viral diseases. Eur J Immunol 1989; 19: 689–94

    Article  PubMed  CAS  Google Scholar 

  41. Sawada M, Suzumura A, Marunouchi T. TNFα induces IL-6 production by astrocytes but not by microglia. Brain Res 1992; 583: 296–9

    Article  PubMed  CAS  Google Scholar 

  42. Kasahara T, Mukaida N, Yamashita K, et al. IL-1 and TNF-α induction of IL-8 and monocyte chemotactic and activating factor (MCAF) mRNA expression in a human astrocytoma cell line. Immunology 1991; 74: 60–7

    PubMed  CAS  Google Scholar 

  43. Nakamura H, Motoyoshi S, Kadokawa T. Anti-inflammatory action of interleukin-1 through the pituitary-adrenal axis in rats. Eur J Pharmacol 1988; 151: 67–73

    Article  PubMed  CAS  Google Scholar 

  44. Darling G, Goldstein DS, Stull R, et al. TNF: immune endocrine interaction. Surgery 1989; 105: 1155–60

    Google Scholar 

  45. Sharp BM, Matta SG, Peterson PK, et al. Tumor necrosis factor-alpha is a potent ACTH secretagogue: comparison to interleukin-1 beta. Endocrinology 1989; 124: 3131–3

    Article  PubMed  CAS  Google Scholar 

  46. Rettori V, Milenkovic L, Beutler BA, et al. Hypothalamic action of cachectin to alter pituitary hormone release. Brain Res Bull 1989; 23: 471–5

    Article  PubMed  CAS  Google Scholar 

  47. Gaillard RC, Turnill D, Sappino P, et al. TNF alpha inhibits the hormonal response of the pituitary gland to hypothalamic releasing factors. Endocrinology 1990; 127: 101–6

    Article  PubMed  CAS  Google Scholar 

  48. Walton PE, Cronin MJ. Tumor necrosis factor-α inhibits growth hormone secretion from cultured anterior pituitary cells. Endocrinology 1989; 125: 925–9

    Article  PubMed  CAS  Google Scholar 

  49. Walton PE, Cronin MJ. Tumor necrosis factor-α and interferon-α reduce prolactin release in vitro. Am J Physiol 1990; 259: E672–6

    PubMed  CAS  Google Scholar 

  50. Pang XP, Hershman JM, Mirell CJ, et al. Impairment of hypothalamic-pituitary-thyroid function in rats treated with human recombinant tumor necrosis factor-alpha (cachectin). Endocrinology 1989; 125: 76–84

    Article  PubMed  CAS  Google Scholar 

  51. Feigin RD, Dodge PR. Bacterial meningitis: newer concepts of pathophysiology and neurologic sequelae. Pediatr Clin North Am 1976; 23: 541–6

    PubMed  CAS  Google Scholar 

  52. Arditi M, Manogue KR, Caplan M, et al. Cerebrospinal fluid cachetin/tumor necrosis factor-α and platelet-activating factor concentrations and severity of bacterial meningitis in children. J Infect Dis 1990; 162: 139–47

    Article  PubMed  CAS  Google Scholar 

  53. Leist TP, Frei K, Kam Hansen S, et al. Tumor necrosis factor alpha in cerebrospinal fluid during bacterial, but not viral, meningitis. Evaluation in murine model infections and in patients. J Exp Med 1988; 167: 1743–8

    Article  PubMed  CAS  Google Scholar 

  54. Mustafa MM, Lebel MH, Ramilo O, et al. Correlation of interleukin-1 beta and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis. J Pediatr 1989; 115: 208–13

    Article  PubMed  CAS  Google Scholar 

  55. McCracken GH Jr, Mustafa MM, Ramilo O, et al. Cerebrospinal fluid interleukin 1-beta and tumor necrosis factor concentrations and outcome from neonatal gram-negative enteric bacillary meningitis. Pediatr Infect Dis J 1989; 8: 155–9

    PubMed  Google Scholar 

  56. Moller B, Mogensen SC, Wendelboe P, et al. Bioactive and inactive forms of tumor necrosis factor-α in spinal fluid from patients with meningitis. J Infect Dis 1991; 163: 886–9

    Article  PubMed  CAS  Google Scholar 

  57. Waage A, Halstensen A, Shalaby R, et al. Local production of tumour necrosis factor α, interleukin 1 and interleukin 6 in meningococcal meningitis. J Exp Med 1989; 170: 1859–67

    Article  PubMed  CAS  Google Scholar 

  58. Mustafa MM, Ramilo O, Olsen KD, et al. Tumor necrosis factor in mediating experimental Haemophilus influenzae type B meningitis. J Clin Invest 1989; 84: 1253–9

    Article  PubMed  CAS  Google Scholar 

  59. Quagliarello VJ, Wispelwey B, Long WJ, et al. Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in the rat. J Clin Invest 1991; 87: 1360–6

    Article  PubMed  CAS  Google Scholar 

  60. Velasco S, Tarlow M, Olsen K, et al. Temperature-dependent modulation of lipopolysaccharide-induced interleukin-1β and tumor necrosis factor-α expression in cultured human astroglial cells by dexamethasone and indomethacin. J Clin Invest 1991; 87: 1674–89

    Article  PubMed  CAS  Google Scholar 

  61. Beutler B, Krochin N, Milsark IW. Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science 1986; 232: 977–80

    Article  PubMed  CAS  Google Scholar 

  62. Odio CM, Faingezicht I, Paris M, et al. The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. N Engl J Med 1991; 324: 1525–31

    Article  PubMed  CAS  Google Scholar 

  63. Saez-Llorens X, Ramilo O, Mustafa, MM. Molecular pathophysiology of bacterial meningitis: current concepts and therapeutic implications. J Pediatr 1990; 116: 671–82

    Article  PubMed  CAS  Google Scholar 

  64. Grau G, Piguet PF, Vassalli P, et al. Tumor necrosis factor and other cytokines in cerebral malaria: experimental and clinical data. Immunol Rev 1989; 112: 50–70

    Article  Google Scholar 

  65. Phillips RE, Solomon T. Cerebral malaria in children. Lancet 1990; 336: 1355–60

    Article  PubMed  CAS  Google Scholar 

  66. Grau GE, Fajardo LF, Piguet PF, et al. Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science 1987; 237: 1210–12

    Article  PubMed  CAS  Google Scholar 

  67. Clark IA, Ilschner S, MacMicking JD, et al. TNF and Plasmodium berghei ANKA-induced cerebral malaria. Immunol Lett 1990; 25: 195–8

    Article  PubMed  CAS  Google Scholar 

  68. Tracey KJ, Fong Y, Hesse DG, et al. Anti-cachetin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature 1987; 330: 662–4

    Article  PubMed  CAS  Google Scholar 

  69. Tracey KJ, Cerami A. TNF: a pleiotropic cytokine and therapeutic target. Annu Rev Med 1993. In press

    Google Scholar 

  70. Gamble JR, Harlan JM, Klebanoff SJ, et al. Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor. Proc Natl Acad Sci USA 1985; 82: 8667–71

    Article  PubMed  CAS  Google Scholar 

  71. Grau GE, Taylor TE, Molyneux ME, et al. Tumor necrosis factor and disease severity in children with falciparum malaria. N Engl J Med 1989; 320: 1586–91

    Article  PubMed  CAS  Google Scholar 

  72. Kwiatkowski D, Cannon JG, Manogue KR, et al. Tumor necrosis factor production in falciparum malaria and its association with schizont rupture. Clin Exp Immunol 1989; 77: 361–6

    PubMed  CAS  Google Scholar 

  73. Bate CAW, Taverne J, Playfair JHL. Malarial parasites induce TNF production by macrophages. Immunology 1988; 64: 227–31

    PubMed  CAS  Google Scholar 

  74. Hafler DA, Weiner HL. MS: a CNS and systemic autoimmune disease. Immunology Today 1989; 10: 104–7

    Article  PubMed  CAS  Google Scholar 

  75. Selmaj K, Raine CS, Cannella B, et al. Identification of lymphotoxin and TNF in MS lesions. J Clin Invest 1991; 87: 949–54

    Article  PubMed  CAS  Google Scholar 

  76. Traugott U, Reinherz EL, Raine CS. Multiple sclerosis: distribution of T cell subsets within active chronic lesions. Science 1993; 219: 308–9

    Article  Google Scholar 

  77. Ben-Nun A, Cohen IR. EAE mediated by T cell lines: process of selection of lines and characterization of the cells. J Immunol 1982; 129: 303–8

    PubMed  CAS  Google Scholar 

  78. Paterson PY. Autoimmunity: genetic, immunologic, virologic, and clinical aspects. In: Talel N, editor. Autoimmune neurological diseases: experimental animal systems and implications for multiple sclerosis. New York: Academic Press, 1977: 643–92

    Google Scholar 

  79. Hofman FM, Hinton DR, Johnson K, et al. Tumor necrosis factor identified in multiple sclerosis brain. J Exp Med 1989; 170: 607–12

    Article  PubMed  CAS  Google Scholar 

  80. Hauser SL, Doolittle TH, Lincoln R, et al. Cytokine accumulations in CSF of multiple sclerosis patients: frequent detection of interleukin-1 and tumor necrosis factor but not interleukin-6. Neurology 1990; 40: 1735–9

    Article  PubMed  CAS  Google Scholar 

  81. Sharief MK, Phil M, Hentges R. Association between tumor necrosis factor-α and disease progression in patients with multiple sclerosis. N Engl J Med 1991; 325: 467–72

    Article  PubMed  CAS  Google Scholar 

  82. Benvenuto R, Paroli M, Buttinelli C, et al. Tumor necrosis factor-alpha synthesis by cerebrospinal-fluid derived T cell clones from patients with multiple sclerosis. Clin Exp Immunol 1991; 84: 97–102

    PubMed  CAS  Google Scholar 

  83. Beck J, Rondot P, Catinot L, et al. Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in multiple sclerosis: do cytokines trigger off exacerbations? Acta Neurol Scand 1988; 78: 318–23

    Article  PubMed  CAS  Google Scholar 

  84. Merrill JE, Strom SR, Ellison GW, et al. In vitro study of mediators of inflammation in multiple sclerosis. J Clin Immunol 1989; 9: 84–96

    Article  PubMed  CAS  Google Scholar 

  85. Jenkins HG, Ikeda H. Tumour necrosis factor causes an increase in axonal transport of protein and demyelination in the mouse optic nerve. J Neurol Sci 1992; 108: 99–104

    Article  PubMed  CAS  Google Scholar 

  86. Ruddle NH, Bergman CM, McGrath KM, et al. An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis. J Exp Med 1990; 172: 1193–1200

    Article  PubMed  CAS  Google Scholar 

  87. Selmaj K, Raine CS, Cross AH. Anti-TNF factor therapy abrogates autoimmune demyelination. Ann Neurol 1991; 30: 694–700

    Article  PubMed  CAS  Google Scholar 

  88. Hartung HP, Heininger K, Schafer B, et al. Immune mechanisms in inflammatory polyneumopathy. Ann N Y Acad Sci 1988; 540: 122–61

    Article  PubMed  CAS  Google Scholar 

  89. Hartung HP, Toyka KV. T-cell and macrophage activation in experimental autoimmune neuritis and Guillain-Barré syndrome. Ann Neurol 1990; 27: 57–63

    Article  Google Scholar 

  90. Sharief MK, McLean B, Thompson EJ. Elevated serum levels of tumor necrosis factor-α in Guillain-Barré syndrome. Ann Neurol 1993; 33: 591–6

    Article  PubMed  CAS  Google Scholar 

  91. Gabuzda DH, Hirsch MS. Neurologic manifestations of infection with human immunodeficiency virus. Ann Intern Med 1987; 107: 383–91

    PubMed  CAS  Google Scholar 

  92. Koenig S, Gendelman HE, Orenstein JM, et al. Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 1986; 1089–93

    Google Scholar 

  93. Wiley CA, Schrier RD, Nelson JA, et al. Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci USA 1986; 83: 7089–93

    Article  PubMed  CAS  Google Scholar 

  94. Grimaldi LME, Martino GV, Franciotta DM, et al. Elevated alpha-tumor necrosis factor levels in spinal fluid from HIV-1-infected patients with central nervous system involvement. Ann Neurol 1991; 29: 21–5

    Article  PubMed  CAS  Google Scholar 

  95. Mintz M, Rapaport R, Oleske JM, et al. Elevated serum levels of tumor necrosis factor are associated with progressive encephalopathy in children with acquired immunodeficiency syndrome. Am J Dis Child 1989; 143: 771–4

    PubMed  CAS  Google Scholar 

  96. Tyor WR, Glass JD, Griffin JW, et al. Cytokine expression in the brain during the acquired immunodeficiency syndrome. Ann Neurol 1992; 31: 349–60

    Article  PubMed  CAS  Google Scholar 

  97. Folks TM, Clouse KA, Justement J, et al. Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone. Proc Natl Acad Sci USA 1989; 86: 2365–8

    Article  PubMed  CAS  Google Scholar 

  98. Israel N, Hazan U, Alcami J, et al. Tumor necrosis factor stimulates transcription of HIV-1 in human T lymphocytes, independently and synergistically with mitogens. J Immunol 1989; 143: 3956–60

    PubMed  CAS  Google Scholar 

  99. Poli G, Bressler P, Kinter A, et al. Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor-α by transcriptional and post-transcriptional mechanisms. J Exp Med 1990; 172: 151–8

    Article  PubMed  CAS  Google Scholar 

  100. Merrill JE, Koyanagi Y, Chen ISY Interleukin-1 and tumor necrosis factor-alpha can be induced from mononuclear phagocytes by human immunodeficiency virus type 1 binding to the CD4 receptor. J Virol 1989; 63: 4404–8

    PubMed  CAS  Google Scholar 

  101. Vyakarnam A, McKeating J, Meager A, et al. Tumor necrosis factor (α,β) induced by HIV-1 in peripheral blood mononuclear cells potentiates virus replication. AIDS 1990; 4: 21–7

    Article  PubMed  CAS  Google Scholar 

  102. VonHanwehr RI, Hofman FM, Taylor CR, et al. Mononuclear lymphoid populations infiltrating the microenvironment of primary CNS tumors. Characterization of cell subsets with monoclonal antibodies. J Neurosurg 1993; 60: 1138

    Google Scholar 

  103. Bethea JR, Gillespie GY, Chung IY, et al. Tumor necrosis factor production and receptor expression by a human malignant glioma cell line, D54-MG. J Neuroimmunol 1990; 30: 1–13

    Article  PubMed  CAS  Google Scholar 

  104. Lachman LB, Brown DC, Dinarello CA. Growth-promoting effect of recombinant interleukin 1 and tumor necrosis factor for a human astrocytoma cell line. J Immunol 1987; 138: 2913–6

    PubMed  CAS  Google Scholar 

  105. Barna BP, Barnett GH, Jacobs BS, et al. Divergent responses of human astrocytoma and non-neoplastic astrocytes to tumor necrosis factor alpha involve the 55 kDa tumor necrosis factor receptor. J Neuroimmunol 1993; 43: 185–90

    Article  PubMed  CAS  Google Scholar 

  106. Yung WKA, Zhang X, Steck PA, et al. Differential amplification of the TGF-α gene in human gliomas. Cancer Commun 1990; 2: 201–5

    PubMed  CAS  Google Scholar 

  107. Liu SKM, Jakowatz JG, Pollack RB, et al. Effects of intracarotid and intravenous infusion of human TNF and LT on established intracerebral rat gliomas. Lymphokine Cytokine Res 1991; 10: 189–94

    PubMed  CAS  Google Scholar 

  108. Kido G, Wright JL, Merchant RE. Acute effects of human recombinant tumor necrosis factor-α on the cerebral vasculature of the rat in both brain and in an experimental glioma model. J Neuro-Oncol 1991; 10: 95–109

    Article  CAS  Google Scholar 

  109. Stewart P, Kayakawa K, Farrell C, et al. Quantitative study of microvessel ultrastructure in human peritumoral brain tissue. J Neurosurg 1987; 67: 697–705

    Article  PubMed  CAS  Google Scholar 

  110. Yoshida J, Wakabayaski T, Mizuno M, et al. Clinical effect of intra-arterial tumor necrosis factor-α for malignant glioma. J Neurosurg 1992; 77: 78–83

    Article  PubMed  CAS  Google Scholar 

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Zimmerman, G.A., Martin, S.B. & Tracey, K.J. The Neuroimmunology of Tumour Necrosis Factor-α. Clin. Immunother. 1, 67–78 (1994). https://doi.org/10.1007/BF03258492

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