SYNERGISTIC ACTIONS OF INTERFERONS AND TUMOR NECROSIS FACTOR

Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.

SYNERGISTIC ACTIONS OF INTERFERONS AND TUMOR NECROSIS FACTOR

Dev Med Virol; 4:353-63 1988. Unique Identifier : AIDSLINE ICDB/89649867
Feinman R; Vilcek J; Dept. of Microbiology, New York Univ. Medical Center, 550 First; Ave., New York, NY 10016

Abstract: Cytotoxic/cytostatic and antitumor actions of tumor necrosis factor (TNF), synergistic enhancement of tumor cell cytotoxicity with TNF and interferons (IFNs), and synergistic antitumor actions of TNF and IFNs are reviewed. Although TNF and lymphotoxin (LT) are known to be directly cytostatic or cytotoxic for tumor cells, the mechanism of action remains poorly understood. Metabolic inhibitors such as actinomycin D and mitomycin C greatly increase the susceptibility of cells to TNF cytotoxicity. In contrast to the inhibitory actions on tumor cells in culture, it is likely that, unless TNF is administered intratumorally, much of the antitumor activity seen with TNF in experimental animals is indirect and not related to the tumor cells' susceptibility to the action of TNF. Many studies have shown that IFNs can enhance the susceptibility of tumor cells to the cytotoxic actions of TNF or LT. The synergism between TNF and IFNs may be related to the ability of both agents to slow progression through the cell cycle. In suppressing cell growth, TNF and IFNs probably activate separate inhibitory pathways whose combined actions are greater than the sum of their separate actions. The potentiating action of IFNs on TNF cytotoxicity might also be related to a somewhat similar action of various inhibitors of RNA and protein synthesis. Like metabolic inhibitors, IFNs might interfere with a putative repair process protecting cells from TNF cytotoxicity. Results of animal experiments are sufficiently encouraging to consider the use of combined therapy with TNF and IFN-gamma in human cancer. This combination is also being considered for the treatment of patients infected with HIV. (51 Refs)

Keywords: Animal Cell Division/DRUG EFFECTS Cell Line Cell Survival/DRUG EFFECTS Drug Synergism Human Interferon Type I/THERAPEUTIC USE Interferon Type II/THERAPEUTIC USE Interferons/*THERAPEUTIC USE Neoplasms/*THERAPY Tumor Cells, Cultured/DRUG EFFECTS Tumor Necrosis Factor/*THERAPEUTIC USE JOURNAL ARTICLE REVIEW REVIEW, TUTORIAL

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