INTERACTION OF IFN ALPHA BETA WITH HOST-CELLS ESSENTIAL TO THE EARLY INHIBITION OF FRIEND-ERYTHROLEUKEMIA VISCERAL METASTASES IN MICE/

We have previously shown that an intact immune system was essential to the increase in survival time of IFN-alpha/beta-treated mice injected i.v. with an IFN-alpha/beta-resistant line of Friend erythroleukemia cells (FLC) highly metastatic to the liver and spleen. Here, we have i nvestigated the early interactions of IFN alpha/beta with host cells p rior to the development of the immune response. IFN alpha/beta treatme nt resulted in 50 to 100-fold inhibition of FLC multiplication in the liver and spleen of normal DBA/2 mice shortly after tumor inoculation, as evaluated by colony formation in agarose. IFN treatment was far le ss effective in inhibiting the multiplication of the FLC in the livers of NK-cell-deficient DBA/2 beige mice, or in immunocompetent DBA/2 mi ce treated with antibody to asialo GMI, or silica, or in mice subjecte d to sub-lethal irradiation. Injection of antibody to CD4 or CD8 did n ot affect the early inhibitory action of IFN alpha/beta on FLC multipl ication but did decrease survival time. Light- and electron-microscope examination of the livers of IFN-treated, FLC-injected mice confirmed the early inhibition of FLC multiplication in the liver and spleen. O ur results indicate that IFN alpha/beta inhibits the development of FL C visceral metastases by acting first on host cells, such as NK cells and macrophages, and then continues to act in consort with the develop ing immune response. (C) 1994 Wiley-Liss, Inc.