Increased serum levels of MIP-1alpha correlate with bone disease and angiogenic cytokines in patients with multiple myeloma.

Many cytokines possess variable roles in the pathogenesis of multiple myeloma. Macrophage inflammatory protein-1alpha (MIP-1alpha) is an osteoclast-activating factor with a major role in myeloma bone disease. The aim of the study was to examine its participation in the angiogenic process of the disease. We measured, by enzyme-linked immunosorbent assays, its serum levels in 56 newly diagnosed myeloma patients, in several skeletal grades and stages of the disease and in 25 healthy controls. Concurrently, we measured serum levels of the angiogenic cytokines basic-fibroblast growth factor, hepatocyte growth factor and interleukin-18. All the above cytokines were higher in myeloma patients (p < 0.001 for all cases) and were increasing in parallel with disease stage (p < 0.001 for all cases) and skeletal grade (p < 0.04 for MIP-1alpha and p < 0.001 for the other cases). Moreover, positive correlations between MIP-1alpha and all the angiogenic cytokines were noted (p < 0.001 for all cases). MIP-1alpha seems to be a predominant factor responsible for the enhancement of bone resorption and increased angiogenesis. The positive correlation between MIP-1alpha and the angiogenic chemoattractants supports the involvement of these factors in the biology of myeloma cell growth. Moreover, they could be used as possible therapeutic targets as well as markers of disease activity.