Synergistic antiproliferative effects of glucocorticoids and interferon-alpha on some lymphoid cell lines.
The Daudi B lymphoblastoid cell line was previously demonstrated to be highly sensitive to the antiproliferative effect of recombinant interferon-alpha A (rIFN-alpha A). In the present study, glucocorticoid hormones were shown to act synergistically with rIFN-alpha A to further increase the sensitivity of Daudi cells to rIFN-alpha A. At 10(-6) M, dexamethasone, prednisolone, or hydrocortisone alone had little effect on Daudi cell growth, but they greatly potentiated the antiproliferative activity of rIFN-alpha A. The synergy between rIFN-alpha A and glucocorticoids on Daudi cells was not related to the inhibitory effects of glucocorticoids on prostaglandin or leukotriene synthesis, since no synergy was observed between rIFN-alpha A and indomethacin or nordihydroguaiaretic acid. Glucocorticoids and rIFN-alpha A also had appreciable synergistic antiproliferative effects on two out of five other IFN-sensitive lymphoid cell lines. When Raji B lymphoblastoid cells, which were quite resistant to the antiproliferative effect of rIFN-alpha A, were treated with the combination of glucocorticoids and rIFN-alpha A, no significant synergistic effects were observed. The synergistic antiproliferative effects of glucocorticoids and rIFN-alpha A observed with some IFN-sensitive lymphoid cell lines in this in vitro study may have clinical relevance in the treatment of certain lymphoid malignancies that are sensitive to rIFN-alpha A therapy.
Elliott
K R
KR
Laboratory of Biochemical Physiology, National Cancer Institute, Frederick Cancer Research Facility, Maryland 21701.
Princler
G L
GL
Urba
W J
WJ
Faltynek
C R
CR
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004357:Drug Synergism; D005938:Glucocorticoids / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007370:Interferon Type I / Q000494:pharmacology*; D008221:Lymphoid Tissue / Q000166:cytology* / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology; D009637:Masoprocol / Q000494:pharmacology; D011994:Recombinant Proteins; D013936:Thymidine / Q000378:metabolism
D005938:Glucocorticoids; D007370:Interferon Type I; D011994:Recombinant Proteins; D009637:Masoprocol; D013936:Thymidine; D007213:Indomethacin