Macrophage inflammatory protein 1-alpha is a potential osteoclast stimulatory factor in multiple myeloma

This study was designed to determine if macrophage inhibitory protein-1 alp ha (MIP-1 alpha), a recently described osteoclast (OCL) stimulatory factor, (1) was present in marrow from patients with multiple myeloma (MM) and poss ibly involved in the bone destructive process. MIP-1 alpha, but not interle ukin-1 beta (IL-1 beta), tumor necrosis factor-beta (TNF-beta), or interleu kin-6 (IL-6), messenger RNA was elevated in freshly isolated bone marrow fr om 3 of 4 patients with MM compared to normal controls. Furthermore, enzyme -linked immunosorbent assays of freshly Isolated bone marrow plasma detecte d increased concentrations of hMIP-1 alpha (range, 75-7784 pg/mL) in 8 of 1 3 patients (62%) with active myeloma, in 3 of 18 patients (17%) with stable myeloma (range, 75-190.3), as well as in conditioned media from 4 of 5 lym phoblastoid cell lines (LCLs) derived from patients with MM, Mildly elevate d levels of MIP-1 alpha were detected in 3 of 14 patients (21%) with other hematologic diagnoses (range, 80.2-118.3, median value of 95 pg/mL) but not in normal controls (8 of 7), MIP-1 alpha was not detected in the periphera l blood of any patients with MM, In addition, recombinant hMIP-1 alpha indu ced OCL formation in human bone marrow cultures. Importantly, addition of a neutralizing antibody to MIP-1 alpha to human bone marrow cultures treated with freshly isolated marrow plasma from patients with MM blocked the incr eased OCL formation induced by these marrow samples but had no effect on co ntrol levels of OCL formation. Thus, high levels of MIP-1 alpha are express ed in marrow samples from patients with MM, but not in marrow from patients with other hematologic disorders or controls, and support an important rol e for MIP-1 alpha as one of the major factors responsible for the increased OCL stimulatory activity in patients with active MM. (C) 2000 by The Ameri can Society of Hematology.