Serum interleukin-17 and its relationship to angiogenic factors in multiple myeloma

Background: Interleukin-17 (IL-17) is a CD4 T-cell-derived mediator of angiogenesis that stimulates vascular endothelial cell migration and regulates the production of a variety of proangiogenic factors, such as tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial cell growth factor (VEGF). Angiogenesis is implicated in the progression of multiple myeloma (MM). Methods: We measured serum levels of IL-17, TNF-alpha, and VEGF, as well as microvessel density (MVD) in 40 untreated MM patients. Results: Levels of IL-17 in the sera of patients with MM were higher than those in matched controls; however, the difference did not reach statistical significance. Serum levels of both TNF-alpha and VEGF in MM patients were significantly higher than those in controls (P<0.001 in both instances). Levels of IL-17 in MM patients, both stage 11 and stage 111, were significantly higher than those of stage I patients (p=0.001 and p<0.001, respectively). Similarly, higher values of VEGF (p<0.001), TNF-a (p<0.001), and MVD (p<0.035) were associated with advanced disease stage. Serum values of IL-17 in MM patients correlated positively not only with VEGF (Spearman’s rho=0.606) and TNF-alpha (r=0.552; p<0.001 in both instances), but also with MVD (r=0.385, p=0.014). In addition, a positive correlation was found between serum values of VEGF and TNF-alpha (r=0.657, p<0.001), MVD and VEGF (r=0.353, p=0.026), and between MVD and TNF-alpha (r=0.506,p=0.001) in MM patients. Conclusion: These results suggest that IL-17 plays a role in the promotion of angiogenesis and associated disease progression in MM. (C) 2006 European Federation of Internal Medicine. Published by Elsevier B.V All rights reserved

Positive correlation between bone marrow mast cell density and ISS prognostic index in patients with multiple myeloma

We evaluated mast cell density (MCD) in myeloma bone marrow biopsies and correlated it with stage of disease and markers of angiogenesis. Fifty-three untreated myeloma patients and 28 of them responded to therapy were studied. Mast cells were highlighted using immunohistochemical stain for tryptase. Angiogenesis was evaluated measuring microvascular density and serum levels of basic-fibroblast growth factor and tumor necrosis factor-alpha. MCD was higher in untreated patients, compared to healthy population and responders. Significant association was found between MCD with angiogenesis and clinical stage of disease, suggesting that mast cells could be used as target for myeloma treatment. (C) 2013 Elsevier Ltd. All rights reserved

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