Tumor Necrosis Factor/Cachectin as an Effector of T Cell-Dependent Immunopathology
Review articleOpen access
1993/01/01 Chapter DOI: 10.1016/B978-0-12-364935-5.50016-X
Publisher SummaryThe possible implications of tumor necrosis factor (TNF) in immunopathological reactions has been investigated only recently. It is likely that TNF is involved at several levels of the immune response. Thus, this chapter describes TNF properties relevant to tissue injury, the role of TNF in T cell-mediated immunopathological reactions in vivo, and the possible cytokine interactions responsible for the overproduction of TNF. One of the characteristics of TNF responsible for its effects observed originally, that is, the induction of hemorrhagic necrosis of tumors, is its numerous and potent effects on vascular endothelial cells. The major effects of TNF in endotoxinemia—such as cerebrovascular lesions in malaria or vascular leak in graft-versus-host disease—may indeed depend largely on the modulatory and toxic effects of TNF on endothelial cells. Another peculiar feature of TNF is its ability to induce concomitantly cellular necrosis and proliferation, which are characteristic alterations of tissue damage and remodeling observed in immunopathological reactions. In vitro, it has been shown that TNF—depending on the dose—can cause either proliferation or necrosis of various cell types. In vivo, administration of recombinant TNF to several species—including man—reproduces the pathological changes of Gram-negative sepsis.
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