RECOMBINANT INTERFERON-GAMMA INHIBITS THE IN-VITRO PROLIFERATION OF HUMAN MYELOMA CELLS

Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma) and dexamet hasone (DEX) have shown anti-tumour effects in multiple myeloma (MM) c ells. Bone marrow plasma cells from 39 MM patients were cultured to cl arify the intensity and specific activity of each compound on bromo-de oxyuridine (BrdUrd) uptake and immunoglobulin (Ig) secretion. BrdUrd u ptake was inhibited by recombinant human IFN-gamma (100 U/ml) and by D EX(10(-6) M). The stimulation index (StI), i.e. labelling index (LI) o f 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 sam ples/controls, was 0.04 (M +/- SEM), P<0.0001, and 0.52 +/- 0.04 (M +/ - SEM), P<0.0001, respectively. Finally, IPN-gamma inhibits BrdUrd upt ake only and LFN-alpha secretion only. In 18 patients the simultaneous addition of IFN-alpha plus IFN-gamma mainly paralleled the effect of IFN-gamma on BrdUrd uptake and IFN-alpha on secretion, but did not res ult in any additive or synergistic effect, though both BrdUrd uptake a nd Ig secretion were decreased to about the same extent as with DEX. T hese data indicate that the combination of IFN-alpha plus IFN-gamma an d DEX are the strongest inhibitors of both BrdUrd uptake and secretion . Since IFN-alpha and IFN-gamma appear to have a different mechanism o f action, their combined use could be considered as a possible new tre atment strategy.