Interleukin 1 autocrine growth system in human multiple myeloma

The role of interleukin 1 (IL 1) in the growth of human multiple myeloma cells was studied in vitro. In the culture supernatant of myeloma cells, IL 1-like activities were detected by the stimulating on murine thymocyte proliferative response and these activities were completely inhibited by anti-IL 1 beta antibody but not by anti-IL 1 alpha antibody. Recombinant human IL 1 alpha (alpha) and IL 1 beta (beta) enhanced the proliferation of myeloma cells freshly isolated from the bone marrow of patients with multiple myeloma. Moreover, the spontaneous growth of myeloma cells was partly inhibited by anti-IL 1 beta antibody but not by anti-IL 1 alpha antibody. IL 1 receptor was detected on the surface of 50% of the myeloma cells by flow cytofluorometric analysis. The expression of IL 1 receptor (IL 1R) on myeloma cells was also analyzed using a binding assay with 125I-labeled IL 1 alpha. By Scatchard plot analysis, two classes of IL 1R were found on the myeloma cells. The major class (2700-7200 sites/cell) had the lower affinity (Kd = 0.88-1.2 x 10(-9) M) and the minor class (70-500 sites/cell) had the higher affinity (Kd = 3.1 - 38.0 x 10(-12) M). Furthermore, a tendency for a proliferation of IL 1R-positive myeloma cells to be induced by adding exogenous IL 1 was observed. These results suggest IL 1 beta to be one of the autocrine growth factors for multiple myeloma cells.