Synergistic effects of alpha interferon and 1,25 dihydroxyvitamin D3: preliminary evidence suggesting that interferon induces expression of the vitamin receptor.
BACKGROUND
To active metabolite of vitamin D3-1,25(OH)2D3-is a well-known differentiation inducer. The addition of this metabolite to sensitive cell cultures inhibits proliferation and induces monocytic-macrophagic differentiation. Alpha interferon may also inhibit proliferation and increase the expression of some surface antigens in some neoplastic cells. In the present report, we describe the synergistic activity of these two drugs on U-937 and on cultured cells from a leukemic patient.


METHODS
Proliferation was studied by 3H-thymidine incorporation; differentiation markers were evaluated immunologically by monoclonal antibodies and by cytochemical tests. Phagocytosis and NBT reduction test were also performed in order to confirm the differentiating properties of these drugs. Finally, the expression of the 1,25(OH)2D3 receptor was evaluated by immunochemical methods.


RESULTS
After culturing these cells for 72 hours in the presence of 1,25(OH)2D3, cell proliferation was reduced and the expression of some phenotypic and functional markers suggested monocytic-macrophagic differentiation. Alpha interferon and 1,25(OH)2D3 synergistically inhibit the proliferation of U-937 cells. Alpha interferon increased the expression of the 1,25(OH)2D3 receptor in U-937 cells.


CONCLUSIONS
The reported results confirm the synergistic activity of INF and 1,25(OH)2D3 on cell proliferation in monoblastic cells. The possible role of the increased expression of the vitamin receptor in cells cultured in the presence of INF is discussed.
Petrini
M
M
Clinica Medica I, Università di Pisa, Italy.
Dastoli
G
G
Valentini
P
P
Mattii
L
L
Trombi
L
L
Testi
R
R
Ambrogi
F
F
Grassi
B
B
D002117:Calcitriol / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004357:Drug Synergism; D006801:Humans; D016130:Immunophenotyping; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D015479:Leukemia, Myelomonocytic, Acute / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology*; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000096:biosynthesis*; D011994:Recombinant Proteins; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D004273:DNA, Neoplasm; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D011994:Recombinant Proteins; D002117:Calcitriol