Interleukin-1 beta rather than lymphotoxin as the major bone resorbing activity in human multiple myeloma

Human myeloma cells were purified from bone marrow aspirates from four patients having advanced myeloma, including one with common acute lymphoblastic leukemia antigen-positive myeloma. All of these myelomas had marked bone lytic lesions. From the culture supernatants of these purified myeloma cells, bone-resorbing activities were significantly revealed by 45Ca-release bone resorption assay, and IL-1 activities were also detected by IL-1 bioassay (mouse thymocyte comitogenic assay). Sandwich enzyme immunoassay for IL-1 alpha or IL-1 beta revealed that IL-1 beta was responsible for IL-1 activity of these culture supernatants. Furthermore, the bone resorbing activities of these culture supernatants were completely neutralized by pretreatment of anti-IL-1 beta, but not anti-IL-1 alpha antibody. By Northern blot analysis, IL-1 beta mRNA was identified from these myeloma cells. Therefore, it is concluded that myeloma cells produce IL-1 beta, which acts as bone-resorbing activity in multiple myeloma.