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 language | English |
|---|---|
| Pages (from-to) | 87-93 |
| Number of pages | 7 |
| Journal | Journal of Interferon and Cytokine Research |
| Volume | 18 |
| Issue number | 2 |
| Publication status | Published - Feb 1998 |
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ASJC Scopus subject areas
- Immunology
- Virology
- Cell Biology
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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 journal › Article
}
TY - JOUR
T1 - IFN-β partially counteracts inhibition of natural killer activity induced by some antitumor agents
AU - Allavena, P.
AU - Giardina, G.
AU - Sen, S.
AU - Colella, G.
AU - Broggini, M.
AU - D'Incalci, M.
PY - 1998/2
Y1 - 1998/2
N2 - 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.
AB - 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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M3 - Article
VL - 18
SP - 87
EP - 93
JO - Journal of Interferon and Cytokine Research
JF - Journal of Interferon and Cytokine Research
SN - 1079-9907
IS - 2
ER -