A review of the cytokine network in multiple myeloma

Abstract

Because many studies have focused on growth factors in multiple myeloma, the study of the cytokine network appears to be useful for this purpose. Interleukin-6 (IL-6) and IL-2 with their soluble receptors (IL-3, IL-4, IL-10, and IL-11) have been examined. Plasma cells may produce IL-6 by an autocrine mechanism whereas a paracrine mechanism is believed to be involved in the production of IL-6 by bone However, the concomitant evaluation of all immunologic parameters could be more useful than the value of a single IL. Serum levels of IL-6, sIL-6R, sIL-2R, and the expression of membrane-bound IL-2 receptors, both on bone marrow plasma cells and on peripheral blood mononuclear cells, are correlated with disease activity and disease stage. In addition, IL-6 and sIL-6R serum levels are believed to be correlated with the duration of disease-free survival because a high serum level at the time of diagnosis is believed to be correlated with a short duration of survival. However, some laboratory parameters may express the same prognostic value as high ␤ 2 microglobulin and lactate dehydrogenase (LDH) serum levels together with a high plasma cell labeling index are correlated with disease activity.Furthermore, if the evaluation is performed at the time of diagnosis, high values of these parameters are correlated with a short disease-free survival. A correlation between laboratory parameters and the serum level of several cytokines was demonstrated. Hence, the real advantage of the prognostic evaluation of cytokines is reserved for patients who do not exhibit uniform results with regard to ␤ 2 microglobulin and LDH serum levels, or, better, for borderline cases. With regard to the differential diagnosis, all immunologic parameters should be evaluated concomitantly rather than separately to confer a real prognostic value to results. Furthermore, a particular relation was found between a high sIL-6R serum level and a poor response to chemotherapy, therefore suggesting the possibility of identifying in advance a subset of patients with a high risk of treatment failure, as has already been demonstrated in other hematologic malignancies.Finally, the majority of studies indicate that interferons are used mainly in the immunotherapy for multiple myeloma, whereas many clinical trials should still be required for the evaluation of the effectiveness of anti-I-L6 antibodies or antiidiotypic vaccines in reference to the eligible patients for these particular therapies.

Mobilization of Myeloma Cells Involves SDF‐1/CXCR4 Signaling and Downregulation of VLA‐4

“…Hence repeated cycles of chemotherapy could result in increased drug resistance and in the spread of the disease. Numerous examples of the role of the microenvironment and IL-6 in the survival and drug resistance of myeloma cells [57][58][59][60] and other B-cell malignancies [61][62] have been reported. Therefore, new strategies for treatment of MM that consider myeloma cells in their microenvironment should be developed, as was previously suggested [63][64].…”

Molecular and Functional Characterization of a Soluble Form of Oncostatin M/Interleukin-31 Shared Receptor

“…We also looked for sOSMR in sera from healthy individuals and from patients suffering from multiple myeloma, a pathology known to induce increased levels of circulating soluble cytokine receptors (41). An average value of 77 ng/ml circulating sOSMR was measured in normal situations that reached a concentration of 288 ng/ml in multiple myeloma patients (Fig.…”

High ratio of Duffy (a+b+) phenotype in patients with multiple myeloma compared to healthy controls

“…There are a lot of cytokines and transcription factors responsible for its pathogenesis, such as Interleukin 6 (IL-6), IL-2 , IL-8, NFkB, IL-1b, IL-3, IL-4, tumour necrosis factor-b (TNF-b), IL-10 and IL-11 [4][5][6]. It is interesting that some of cytokines and transcription factors have major roles in the pathogenesis of MM are closely related to DARC, especially IL-8, NF-kB, IL-1b and MCP-1 which are some of the chemokines bind to DARC [7].…”