Interleukin-6 sensitizes multiple myeloma cell lines for apoptosis inducedby interferon-alpha

Objective. Interleukin-6 (IL-6) is a multifunctional cytokine affecting gro wth and survival of normal B cell lineage and multiple myeloma cells. To te st the hypothesis that IL-6, as well as other hematopoietic growth factors, may enhance apoptosis of target cells, we investigated the effect of IL-6 on myeloma cells in the presence of IFN-alpha, which is prescribed for pati ents with multiple myeloma. Materials and Methods. Four myeloma cell lines, PCM6, NOP-2, U266, RPM18226 were tested. We determined the induction of apoptosis by flow cytometry, u sing an FITC-Annexin V. Results. IFN-alpha induced apoptosis on myeloma cell lines, and this apopto sis was further enhanced in the presence of IL-6, via activation of caspase 3. During induction of this apoptosis, the expression of c-Myc and Fas inc reased. The addition of IL-6 further increased the expression of Fas, but n ot that of c-Myc. Bcl-2, Bcl-x, and p53 were not affected by the addition o f IL-6 and/or IFN-alpha. Addition of a PI-3-K inhibitor interfered with the enhancing effect of IL-6 on the apoptosis induced by IFN-alpha. Conclusion. We propose that IL-6 has the death signal, as well as growth pr omoting effects, and that PI-3-K may play a key role in the induction of ap optosis by IL-6. (C) 2000 International Society for Experimental Hematology . Published by Elsevier Science Inc.