Identification of Two Groups of Smoldering Multiple Myeloma Patients Who Are Either High or Low Producers of Interleukin-1

Interleukin-1β (IL-1β) is abnormally expressed by the plasma cells obtained from myeloma patients, and it is a potent inducer of the important myeloma growth factor, IL-6. We investigated whether levels of IL-1β biologic activity might distinguish different groups of patients with smoldering multiple myeloma (SMM). We measured the ability of IL-6 production by bone marrow stromal cells to serve as a surrogate marker for IL-1β biologic activity. Using this IL-1β bioassay, we found that it is sensitive at < 1 pg/ml of recombinant IL-1β and that IL-1β biologic activity is detectable with either mature or pro-IL-1β-transduced myeloma cell lines. Patients with active myeloma induced quantitatively higher levels of stromal cell IL-6 production when compared with those with monoclonal gammopathy of undetermined significance (MGUS). The bioassay distinguished two groups of SMM patients, those who were high producers, similar to patients with active MM, and those who were low producers, comparable to MGUS patients. IL-1 antagonists inhibited the paracrine IL-6 production by ≥90% in the majority of patients with an elevated IL-6 level. Based on such studies, it may be possible to predict patients that will progress to active MM and to delay or prevent this progression with IL-1 antagonists.