Effect of antineoplastic agents on gamma-interferon production in human peripheral blood mononuclear cells.
Since gamma-interferon (IFN-gamma) 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-gamma production. Induction of peripheral blood mononuclear cells from normal donors in the presence and absence of various antineoplastic agents was achieved using phytohemagglutinin (8 micrograms/ml). Supernatants 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-gamma production if added within 24 hr after the phytohemagglutinin. The suppression of IFN-gamma production occurred with hydrocortisone concentrations as low as 0.65 microgram/ml, was associated with a diminished proliferative response to the lectin, and occurred with other interferon inducers including staphylococcal enterotoxin A. Adriamycin (0.4 microgram/ml) and vincristine (0.08 microgram/ml) also diminished IFN-gamma 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-gamma. These results are significantly different from experiments previously reported using alpha- and beta-interferons and suggest an important mechanism by which these drugs can produce immunosuppression.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000097:blood; D007700:Kinetics; D015122:Mercaptopurine / Q000494:pharmacology; D008727:Methotrexate / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; D007376:Interleukin-2; D014750:Vincristine; D004317:Doxorubicin; D007371:Interferon-gamma; D015122:Mercaptopurine; D005472:Fluorouracil; D006854:Hydrocortisone; D008727:Methotrexate