The effect of alpha and gamma-interferon on proliferation and production of IgE and beta 2-microglobulin in the human myeloma cell line U-266 and in an alpha-interferon resistant U-266 subline.
An IFN-resistant subline (U-266r alpha) was established from the IFN-alpha-sensitive myeloma cell line U-266 by subculturing U-266 cells with increasing doses of INF-alpha. The U-266r alpha secreted IgE at a higher rate than the U-266 (7.2 X 10(-13) g/c/8 h as compared to 3.3 X 10(-13) g/c/8 h). The 2 cell lines were found to be equally high producers of beta 2m (9.2 and 9.6 X 10(-13) g/c/8 h). The U-266 produced 2.9 times less IgE and 5 times more beta 2m compared to the initial production rates at establishment. INF-alpha and recombinant IFN-alpha 2 (rIFN-alpha 2) inhibited proliferation and concomitantly decreased the rate of IgE and beta 2m secretion in U-266 but not in U-266 IFNr alpha, which in contrast was slightly stimulated by IFN-alpha with respect to growth, IgE and beta 2m secretion. In addition, IFN-alpha at a concentration of 100 U/ml was shown to decrease the IgE and beta 2m production without exerting more than minimal cytotoxicity on U-266 cells. No antiproliferative effect was found for IFN-gamma or recombinant IFN-gamma (rIFN-gamma) on either of the 2 cell lines. IFN-gamma and rIFN-gamma were, however, found to stimulate the production of beta 2m. Our results show that the U-266 and the derived IFN-alpha-resistant subline can be used as models for studying some of the biological effects of IFN-alpha and -gamma in vitro. The clinical implications of these in vitro results, in particular the usefulness of serum determinations of immunoglobulin and beta 2m concentrations for monitoring the tumor cell mass, are discussed.
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000032:analysis / Q000096:biosynthesis*; D007370:Interferon Type I / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000627:therapeutic use*; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D001613:beta 2-Microglobulin / Q000032:analysis / Q000096:biosynthesis*
D007070:Immunoglobulin A; D007370:Interferon Type I; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D007073:Immunoglobulin E; D007371:Interferon-gamma