Production of Interleukin 1β, a Potent Bone Resorbing Cytokine, by Cultured Human Myeloma Cells

Supernatants of freshly isolated human myeloma cell cultures were examined both for bone-resorbing activity (BRA) in vitro using newborn mouse calvaria, and for identification of the causal substances of the BRA. Eight of 14 culture supernatants of myeloma cells had BRA. All of these BRA-positive supernatants were from patients with marked destructive bone lesions of multiple myeloma. The presence of interleukin 1 (IL-1), especially IL-1β, was demonstrated in seven of these BRA-positive supernatants but not in BRA-negative supernatants. The concentrations of IL-1β were high enough to induce bone resorption in the newborn mouse calvaria assay and the BRA was totally abolished by pretreatment of the supernatants with anti-IL-1β antibody but not with either anti-IL-1α antibody or normal serum. Other bone resorbing cytokines such as tumor necrosis factor or lymphotoxin were not present in high enough concentrations to stimulate bone resorption and their levels did not correlate with the BRA. IL-1β mRNA was also identified in BRA-positive myeloma cells. These results demonstrate that IL-1β is the principal agent of BRA present in supernatants of myeloma cell cultures, and also identify a possible role of IL-1β in destructive bone lesions in patients with multiple myeloma.