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A dual anti-tumor effect of a combination of interferon-alpha or interleukin-2 and 5-fluorouracil on natural killer (NK) cell-mediated cytotoxicity.


Clin Immunol Immunopathol. 1992 Jan;62(1 Pt 1):103-11. Unique Identifier

Previous in vitro and in vivo studies have shown a synergism between interferon (IFN) and 5-fluorouracil (5-FU) against different tumor cell lines. In the present study we report that the combination of IFN-alpha and 5-FU has a significant effect not only on the inhibition of tumor cell growth but also on the regulation of natural killer cell-mediated cytotoxicity (NK-CMC). The addition of 5-FU to effector cell population neither affects NK cell activity nor activation of NK cells by IFN or by interleukin (IL)-2. However, pretreatment of target cells with 5-FU increased their susceptibility to NK activity and abolished the protective effect induced by IFN against NK-CMC. This dual effect of IFN-alpha and 5-FU was found to be applicable to target cells of different origins including a cervical carcinoma cell line (ME-180), a hairy cell leukemia-like cell line (Eskol), a CML cell line (K-562) and a primary culture of AIDS-related Kaposi's sarcoma cells. Similar results were found with IL-2 treatment of Eskol cells but not other cells. Combination of IL-2 with 5-FU resulted in enhancement of the sensitivity of the cells to NK activity and abolished the protection against NK-CMC. Based on these results we propose that the combination of IFN-alpha and 5-FU not only has a direct growth inhibitory effect on tumor cells but also has a regulatory role on the immunological arm of the NK-CMC. Moreover, since the combination gave the same pattern of response in different tumor cells, both NK-sensitive and NK-resistant, this combination treatment may be a candidate for clinical trials in various types of tumors.

Cell Division/DRUG EFFECTS Cytotoxicity, Immunologic/*DRUG EFFECTS Drug Synergism Fluorouracil/*ADMINISTRATION & DOSAGE/PHARMACOLOGY Human Interferon-alpha/*ADMINISTRATION & DOSAGE/PHARMACOLOGY Interleukin-2/*ADMINISTRATION & DOSAGE/PHARMACOLOGY Killer Cells, Lymphokine-Activated/DRUG EFFECTS Killer Cells, Natural/*DRUG EFFECTS/IMMUNOLOGY RNA/METABOLISM Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. JOURNAL ARTICLE


Information in this article was accurate in April 30, 1992. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.