Local and systemic response of mice to interferon-alpha 1-transfected Friend leukemia cells.
DBA/2 mice were injected subcutaneously with an interferon (IFN)-alpha/beta-resistant line of Friend erythroleukemia cells (FLC) transfected with the mouse IFN-alpha 1 gene. These tumor cells produced IFN constitutively, and mice had persistently high levels of IFN in the circulation. We examined the IFN-induced host mechanisms responsible for the local inhibition of growth of these IFN-alpha-transfected FLC and some of the unusual systemic effects of constant interferonemia such as extramedullary hematopoiesis in the liver, an increase in myeloid cells in the spleen, and persistently elevated splenic natural killer (NK) cell activity. In addition, both DBA/2 +/bg and beige mice developed a rapid and specific resistance to intravenous challenge with parental FLC. In previous experiments DBA/2 beige mice could not be protected by exogenous IFN-alpha/beta. The differences in the response of mice to the constitutive production of IFN-alpha by IFN-alpha-transfected tumor cells and their response to exogenous IFN is discussed in terms of the effects of IFN on the host and of antitumor therapy.
Gabriele
L
L
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
Kaido
T
T
Woodrow
D
D
Moss
J
J
Ferrantini
M
M
Proletti
E
E
Santodonato
L
L
Rozera
C
C
Maury
C
C
Belardelli
F
F
D000818:Animals; D004351:Drug Resistance / Q000235:genetics; D007121:Immunocompetence; D007167:Immunotherapy; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000235:genetics* / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology* / Q000628:therapy; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA / Q000235:genetics; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014162:Transfection; D014407:Tumor Cells, Cultured
D016898:Interferon-alpha