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
Since its isolation by Carswell et al. in 1975  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 . The successful cloning of TNF-α DNA in 1985  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 . TNF-α may also be directly cytotoxic for tumor cells through stimulation of the production of oxygen radicals in the cells themselves .
KeywordsCorpus Callosum Contralateral Hemisphere Glioma Model Human Tumor Necrosis Factor Hemorrhagic Necrosis
Unable to display preview. Download preview PDF.
- 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.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.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