IFN-β partially counteracts inhibition of natural killer activity induced by some antitumor agents

P. Allavena, G. Giardina, S. Sen, G. Colella, M. Broggini, M. D'Incalci

Research output: Contribution to journalArticle

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Abstract

We investigated whether recombinant human (rHu-IFN-β) (IFN-β) could counteract the inhibition of natural killer (NK) activity caused by antitumor agents. Peripheral blood lymphocytes (PBL) were incubated with different antitumor agents alone or in combination with IFN-β for 3 days and then tested in a cytotoxicity assay against the K562 cell line. The following drugs were used, all of which caused a dose-dependent inhibition of NK activity: etoposide, camptothecin, doxorubicin, cis-DDP, tallimustine, and L- PAM. Concomitant treatment with (1000 U/ml) IFN-β counteracted the inhibitory effect of etoposide and camptothecin but had no consistent effect on the inhibition mediated by the other drugs. Mean values of inhibition of NK activity at 1 μM camptothecin was 48% ± 3.4% and with IFN-β was 10% ± 4.9%. With 100 μM etoposide, mean value of inhibition was 78% ± 3.3%, and with IFN-β, it was 18% ± 1.5%. Cell viability, assessed by vital dye exclusion, and drug uptake, assessed with radiolabeled etoposide, were similar in cells treated with or without IFN-β. The protective effect of IFN-β on NK function was rather selective, as IFN-β did not counteract the drug-mediated inhibition of PBL proliferation when stimulated by phytohemagglutinin (PHA). Other cytokines, IFN-α, IFN-ν, and interleukin-2 (IL-2), had similar protective effect, although IFN-β was slightly more potent. On the other hand, IL-6, a cytokine sharing some properties with IFNs was ineffective. Camptothecin inhibited the expression of mRNA for granzyme B, a lytic protein involved in lymphoid-mediated cytotoxicity. Combined treatment with IFN-β restored-at least in part-the transcription of granzyme B mRNA. These results show that the immunosuppressive effect of some antitumor agents could be partly counteracted by treatment with IFN-β.

Original languageEnglish
Pages (from-to)87-93
Number of pages7
JournalJournal of Interferon and Cytokine Research
Volume18
Issue number2
Publication statusPublished - Feb 1998

Fingerprint

Camptothecin
Etoposide
Antineoplastic Agents
Granzymes
Pharmaceutical Preparations
Lymphocytes
Cytokines
Messenger RNA
Melphalan
K562 Cells
Phytohemagglutinins
Immunosuppressive Agents
Doxorubicin
Interleukin-2
Interleukin-6
Cell Survival
Coloring Agents
Cell Line
Proteins

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Cell Biology

Cite this

IFN-β partially counteracts inhibition of natural killer activity induced by some antitumor agents. / Allavena, P.; Giardina, G.; Sen, S.; Colella, G.; Broggini, M.; D'Incalci, M.

In: Journal of Interferon and Cytokine Research, Vol. 18, No. 2, 02.1998, p. 87-93.

Research output: Contribution to journalArticle

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abstract = "We investigated whether recombinant human (rHu-IFN-β) (IFN-β) could counteract the inhibition of natural killer (NK) activity caused by antitumor agents. Peripheral blood lymphocytes (PBL) were incubated with different antitumor agents alone or in combination with IFN-β for 3 days and then tested in a cytotoxicity assay against the K562 cell line. The following drugs were used, all of which caused a dose-dependent inhibition of NK activity: etoposide, camptothecin, doxorubicin, cis-DDP, tallimustine, and L- PAM. Concomitant treatment with (1000 U/ml) IFN-β counteracted the inhibitory effect of etoposide and camptothecin but had no consistent effect on the inhibition mediated by the other drugs. Mean values of inhibition of NK activity at 1 μM camptothecin was 48{\%} ± 3.4{\%} and with IFN-β was 10{\%} ± 4.9{\%}. With 100 μM etoposide, mean value of inhibition was 78{\%} ± 3.3{\%}, and with IFN-β, it was 18{\%} ± 1.5{\%}. Cell viability, assessed by vital dye exclusion, and drug uptake, assessed with radiolabeled etoposide, were similar in cells treated with or without IFN-β. The protective effect of IFN-β on NK function was rather selective, as IFN-β did not counteract the drug-mediated inhibition of PBL proliferation when stimulated by phytohemagglutinin (PHA). Other cytokines, IFN-α, IFN-ν, and interleukin-2 (IL-2), had similar protective effect, although IFN-β was slightly more potent. On the other hand, IL-6, a cytokine sharing some properties with IFNs was ineffective. Camptothecin inhibited the expression of mRNA for granzyme B, a lytic protein involved in lymphoid-mediated cytotoxicity. Combined treatment with IFN-β restored-at least in part-the transcription of granzyme B mRNA. These results show that the immunosuppressive effect of some antitumor agents could be partly counteracted by treatment with IFN-β.",
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