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Recombinant interferon-gamma inhibits the in vitro proliferation of human myeloma cells
A Palumbo1, S Battaglio, P Napoli
1Dipartimento di Medicina e Oncologia Sperimentale, Ospedale Molinette, Torino, Italy.
Abstract:
Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma) and dexamethasone (DEX) have shown anti-tumour effects in multiple myeloma (MM) cells. Bone marrow plasma cells from 39 MM patients were cultured to clarify the intensity and specific activity of each compound on bromo-deoxyuridine (BrdUrd) uptake and immunoglobulin (Ig) secretion. BrdUrd uptake was inhibited by recombinant human IFN-gamma (100 U/ml) and by DEX (10(-6) M). The stimulation index (StI), i.e. labelling index (LI) of treated samples/controls, was 0.49 +/- 0.09 (mean +/- standard error of the mean, M +/- SEM), P = 0.0003, and 0.52 +/- 0.07 (M +/- SEM), P < 0.0001, respectively. Ig secretion was reduced by IFN-alpha (100 U/ml) and DEX. The secretion index (SI), i.e. Ig quantitation of treated samples/controls, was 0.04 (M +/- SEM), P < 0.0001, and 0.52 +/- 0.04 (M +/- SEM), P < 0.0001, respectively. Finally, IFN-gamma inhibits BrdUrd uptake only and IFN-alpha secretion only. In 18 patients the simultaneous addition of IFN-alpha plus IFN-gamma mainly parallel the effect of IFN-gamma on BrdUrd uptake and IFN-alpha on secretion, but not result in any additive or synergistic effect, though both BrdUrd uptake and Ig secretion were decreased to about the same extent as with DEX. These data indicate that the combination of IFN-alpha plus IFN-gamma and DEX are the strongest inhibitors of both BrdUrd uptake and secretion. Since IFN-alpha and IFN-gamma appear to have a different mechanism of action, their combined use could be considered as a possible new treatment strategy.
Insights
Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), and dexamethasone (DEX) inhibit multiple myeloma (MM) cell proliferation and immunoglobulin secretion. Combining these agents shows potential as a novel MM treatment strategy.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Multiple myeloma (MM) is a cancer of plasma cells.
- Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), and dexamethasone (DEX) have demonstrated anti-tumour properties against MM cells.
Purpose of the Study:
- To evaluate the efficacy of IFN-alpha, IFN-gamma, and DEX on bromo-deoxyuridine (BrdUrd) uptake and immunoglobulin (Ig) secretion in MM cells.
- To explore the potential of combined therapies for MM treatment.
Main Methods:
- Bone marrow plasma cells from 39 MM patients were cultured.
- Cells were treated with IFN-alpha, IFN-gamma, and DEX individually and in combination.
- Bromo-deoxyuridine (BrdUrd) uptake and immunoglobulin (Ig) secretion were measured.
Main Results:
- IFN-gamma and DEX significantly inhibited BrdUrd uptake (P < 0.0003).
- IFN-alpha and DEX significantly reduced Ig secretion (P < 0.0001).
- Combined IFN-alpha and IFN-gamma showed additive effects, with DEX demonstrating the strongest inhibition of both parameters.
Conclusions:
- IFN-alpha and IFN-gamma exhibit distinct mechanisms of action, targeting Ig secretion and BrdUrd uptake, respectively.
- The combination of IFN-alpha, IFN-gamma, and DEX represents a potent strategy for inhibiting MM cell proliferation and function.
- Further investigation into this combination therapy is warranted for potential clinical application in multiple myeloma.