Advertisement

Acute Effects of the Human Recombinant Tumor Necrosis Factor (rTNF) on the Cerebral Vasculature of the Rat in Both Normal Brain and an Experimental Glioma Model

  • Goro Kido
  • Saburo Nakamura
  • Takashi Tsubokawa
  • Randall E. Merchant
  • Harold F. Young

Abstract

Since its isolation by Carswell et al. in 1975 [1] as the agent responsible for hemorrhagic necrosis of sarcoma, the tumor necrosis factor (TNF-α) has been implicated in a variety of physiological activities. Studies in animal models and humans have shown that at least one of the cytokine’s antitumor actions is mediated through these inflammatory mechanisms, leading to hemorrhagic necrosis of tumors [2]. The successful cloning of TNF-α DNA in 1985 [3] and production of recombinant TNF-α (rTNF-α) was followed by an increase in research to more clearly define the specific actions of the cytokine. In vitro, rTNF-α was shown to increase neutrophil adherence to endothelial cells, induce an adhesion-dependent migration of neutrophils through endothelial monolayers, enhance endothelial susceptibility to neutrophil-mediated killing, and stimulate neutrophil respiratory burst and degranulation [4,5]. The mechanism of TNF-α’s action, therefore, is thought to be through neutrophils which, when stimulated by TNF-α, release H2O2, resulting in the production of tissue-damaging oxygen radicals [6]. TNF-α may also be directly cytotoxic for tumor cells through stimulation of the production of oxygen radicals in the cells themselves [7].

Keywords

Corpus Callosum Contralateral Hemisphere Glioma Model Human Tumor Necrosis Factor Hemorrhagic Necrosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B (1975) An endotoxin-induced serum factor that causes necrosis of tumors. Proc Nat Acad Sci USA 72: 3666–3670PubMedCrossRefGoogle Scholar
  2. 2.
    Asher A, Mule JJ, Reichert CM, Shiloni E, Rosenberg SA (1987) Studies on the anti-tumor efficacy of systemically administered recombinant tumor necrosis factor against several murine tumors in vivo. J Immunol 138: 963–974PubMedGoogle Scholar
  3. 3.
    Shirai T, Tamaguchi H, Ito H, Todd CW, Wallance B (1985) Cloning and expression in Escherichia coli of the gene for human tumor necrosis factor. Nature 313: 803–806PubMedCrossRefGoogle Scholar
  4. 4.
    Moser R, Schleiffenbaum B, Groscurth P, Fehr J (1989) Interleukin 1 and tumor necrosis factor stimulate human vascular endothelial cells to promote transendothelial neutrophil passage. J Clin Invest 83: 444–455PubMedCrossRefGoogle Scholar
  5. 5.
    Varani J, Bendelow MJ, Sealey DE, Kunkel SL, Gannon DE, Ryan US, Ward PA (1988) Tumor necrosis factor enhances susceptibility of vascular endothelial cells to neutrophil-mediated killing. Lab Invest 59: 292–295PubMedGoogle Scholar
  6. 6.
    Shau H (1988) Characteristics and mechanism of neutrophil-mediated cytostasis induced by tumor necrosis factor. J Immunol 141: 234–240PubMedGoogle Scholar
  7. 7.
    Neal ML, Fiera RA, Matthews N (1988) Involvement of phospholipase A2 activation in tumor cell killing by tumor necrosis factor. Immunology 64: 81–85Google Scholar
  8. 8.
    Kimura K, Taguchi T, Urushizaki I, Ohno R, Abe O, Furue H, Hattori T, Ichihashi I, Inoguchi K, Majima H, Niitani H, Ota K, Saito T, Suga S (1987) The A-TNF Cooperative Study Group: Phase I study of recombinant human tumor necrosis factor. Cancer Chemother Pharmacol 20: 223–229PubMedCrossRefGoogle Scholar
  9. 9.
    Flectcher WH, Shiu WW, Ishada TA, Haviland DL, Ware CF (1987) Resistance to the cytolytic action of lymphotoxin and tumor necrosis factor coincides with the presence of gap junctions uniting target cells. J Immunol 139: 956–962Google Scholar
  10. 10.
    Selmaji KW, Raine CS (1988) Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol 23: 339–346CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 1991

Authors and Affiliations

  • Goro Kido
    • 1
  • Saburo Nakamura
    • 1
  • Takashi Tsubokawa
    • 1
  • Randall E. Merchant
    • 2
  • Harold F. Young
    • 2
  1. 1.Department of Neurological Surgery, School of MedicineNihon UniversityItabashi-Ku, Tokyo, 173Japan
  2. 2.Department of Surgery, Division of Neurosurgery, Medical College of VirginiaVirginia Commonwealth University RichmondUSA

Personalised recommendations