LOCAL AND SYSTEMIC RESPONSE OF MICE TO INTERFERON-ALPHA-1-TRANSFECTEDFRIEND-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 const itutively, and mice had persistently high levels of IFN in the circula tion. 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 ex tramedullary hematopoiesis in the liver, an increase in myeloid cells in the spleen, and persistently elevated splenic natural killer (NK) c ell activity, In addition, both DBA/2 +/bg and beige mice developed a rapid and specific resistance to intravenous challenge with parental F LC. In previous experiments DBA/2 beige mice could not be protected fl y exogenous IFN-alpha/beta. Tbe differences in the response of mice to the constitutive production of IFN-alpha by IFN-alpha-transfected tum or cells and their response to exogenous IFN is discussed in terms of the effects of IFN on the host and of antitumor therapy.