Since γ-interferon (IFN-γ) is a potent immunomodulator and patients receiving certain antineoplastic agents are at risk of unusual infections, we have determined the effect of certain antineoplastic agents on IFN-γ production. Induction of peripheral blood mononuclear cells from normal donors in the presence and absence of various antineoplastic agents was achieved using phytohemagglutinin (8 µg/ml). Supermatants were then separated by centrifugation, dialyzed, and assayed for interferon. Cell viability was always greater than 85% with or without the presence of drugs. Hydrocortisone was found to eliminate IFN-γ production if added within 24 hr after the phytohemagglutinin. The suppression of IFN-γ production occurred with hydrocortisone concentrations as low as 0.65 µg/ml, was associated with a diminished proliferative response to the lectin, and occurred with other interferon inducers including staphylococcal enterotoxin A.
Adriamycin (0.4 µg/ml) and vincristine (0.08 µg/ml) also diminished IFN-γ production, but only if the peripheral blood mononuclear cells were pretreated with the drugs.
Methotrexate, 5-fluorouracil, and 6-mercaptopurine failed to influence the yield of IFN-γ.
These results are significantly different from experiments previously reported using α- and β-interferons and suggest an important mechanism by which these drugs can produce immunosuppression.
This research was supported by a grant from the KROC Foundation and a grant from the Alaska Cancer Research Telethon through the American Cancer Society.