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Effect of Antineoplastic Agents on -Interferon Production in Human Peripheral Blood Mononuclear Cells¹

Divisions of Infectious Diseases [T. C. C.], Hematology [L. M. S.], and Immunology [S. G.], Department of Medicine, University of California Irvine, Orange, California 92668; Division of Infectious Diseases, Department of Medicine, Marshall University, Huntington, West Virginia 25701 [G. J. G.]; and American Red Cross, Orange County California Division, Santa Ana, California 92705 [H. S. K.]

Since -interferon (IFN-) 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- 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- production if added within 24 hr after the phytohemagglutinin. The suppression of IFN- 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- 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-.

These results are significantly different from experiments previously reported using - and ß-interferons and suggest an important mechanism by which these drugs can produce immunosuppression.

¹ 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.

² To whom requests for reprints should be addressed, at Department of Medicine, University of California Irvine Medical Center, 101 City Drive South, Orange, CA 92668.

Received 4/ 9/84. Accepted 7/31/84.

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