Interleukin-10 Induces Both Plasma Cell Proliferation and Angiogenesis in Multiple Myeloma

Abstract

In multiple myeloma the angiogenic process is enhanced by various mediators. Among them interleukin-10 (IL-10), secreted mainly by myeloma-associated macrophages seems to participate in myeloma progression with variable manners. The aim of the study was to measure serum levels of IL-10 in various stages of MM patients and to correlate them with various angiogenic cytokines, such as vascular endothelial growth factor and angiopoietin-2 and with known proliferation parameters, such as serum levels of B-cell activating factor and bone marrow infiltration by myeloma plasma cells, in order to explore their clinical significance. We measured serum levels of the above parameters by ELISA in 54 newly diagnosed MM patients. All of them were higher in MM patients and were increasing in parallel with disease progression. Furthermore, IL-10 correlated positively with both angiogenic cytokines and proliferation markers. This correlation of IL-10 with both angiogenic cytokines and markers of disease activity implicates that they all have an important role in MM pathogenesis and progression.

Peripheral Inflammation,Apolipoprotein E4, and Amyloid-β Interact to Induce Cognitive and Cerebrovascular Dysfunction

“…The first (C2; G-CSF, IL-10, and RANTES) included cytokines that were higher in LPS-treated mice that express APOE4 (E4FAD+ and E4FAD− mice) compared to the PBS group. RANTES promotes angiogenesis (Wang et al., 2006; Matsuo et al., 2009; Suffee et al., 2012; Liu et al., 2015a), while G-CSF and IL-10 have been demonstrated to both protect/maintain and disrupt the vasculature (Kohno et al., 2003; Dace et al., 2008; Tura et al., 2010; Kawabe et al., 2011; Alexandrakis et al., 2015; Cates et al., 2015; Liu et al., 2015a, 2015b; Wei et al., 2017). Therefore, it is possible that the C2 cytokines initiated angiogenic signaling in E4FAD+ and E4FAD− mice, without maturing into stable vessels, or induced direct brain endothelial cell disruption in a chronic setting.…”

Tumor-associated macrophages and extracellular matrix metalloproteinase inducer in prognosis of multiple myeloma

“…4 5 In addition to promoting an immunosuppressive environment, a pro-tumoral role of M2φ is ascribed to secretion of factors like IL-6 and IL-10. IL-10 secreted mainly by the M2φ is a myeloma growth factor 6 and was recently shown to enhance angiogenesis in MM through VEGF secretion 7 . In addition to the cytokines, CD147 which is an Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) is also implicated in MM tumor progression with levels increasing from benign to malignant disease 8 .…”

Bone marrow micro-environment is a crucial player for myelomagenesis and disease progression

“…IL-10 has been proven to inhibit various immune functions, such as macrophage activation, cytokine production, and antigen presentation [168], while it induces both plasma cell proliferation and angiogenesis in MM [169]. IL-10 is also involved in initiating and promoting other malignancies [170].…”