The Synergistic Effect of Human Recombinant Interferon-α_<2a> in Combination with Interferon-γ and the Induction of Interferon-α_<2a> Receptor by Interferon-γ

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An in vitro examination was made of the synergistic antiproliferative effect of recombinant interferon-γ (IFN-γ) with interferon-α_<2a> (IFN-α_<2a>) on human tumor cell lines, including lung small cell carcinoma QG-90,amelanotic melanoma HMV-1,renal carcinoma ACHN and Burkit lymphoma Daudi. Sixty-four percent of HMV-1 cells and 75% of ACHN cells seeded were killed by treatment with 10 pM and 1000 pM of IFN-γ, respectively. Furthermore, 69% of HMV-1 cells and 59% of ACHN cells were killed by 1000 pM of IFN-α_<2a>. When HMV-1 was treated first with 10 pM of IFN-γ, and then with 1000 pM of IFN-α_<2a>, 81% of cells seeded were killed (p<0.001). Similarly, 89% of ACHN cells were killed by the same sequential treatment with 1000 pM of IFN-γ, and then of IFN-α_<2a> (p<0.001). However, adverse sequence of treatment could not produce such a synergistic result. On the surface of these susceptible cells, HMV-1 and ACHN, to both IFNs, the number of receptors for IFN-α_<2a> increased significantly after treatment with IFN-γ without any serious change of the dissociation constant, suggesting that increase in the number of receptors for IFN-α_<2a> may be the major mechanism of the synergistic effects of IFN-γ with IFN-α_<2a>.
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