| Objective:Multiple myeloma (multiple myeloma, MM) is a malignant proliferation disease of plasma cell, clonal plasma cells in bone marrow is dysplasia, and secrete a monoclonal immunoglobulin or its fragments (M protein), leading to the related organ or tissue injury (ROTI). One of the prominent clinical features is bone destruction, such as osteoporosis, osteolytic lesions and pathologic fractures. The current study found that the bone marrow microenvironment is critical to the growth of myeloma cells, such as the cytokine IL-6, TGF-beta, IL-1β, etc. play an important role in the growth of myeloma cells and activation of osteoclasts. Further study found that IL-6and TGF-β play an important role in the differentiation of Th17cells. IL-17secreted by Th17cells is a powerful proinflammatory cytokine, Series of reactions may caused when IL-17binding with its receptor(IL-17R), such as specific transcription factor may induced by signal transduction, and then priming the transcription of related target genes, which may cause the expression of many inflammatory cytokines, such as IL-6、IL-8, thereby promoting the growth of myeloma cells and activation of osteoclasts, and the activitied osteoclasts will inhibit osteoblast activity and release lots of growth factors, such as IL-6, those factors will promote the survival and growth of myeloma cells, resulting in a vicious circle between the growth of myeloma cells and the activity of osteoclasts. To further understand the role of IL-17in the pathogenesis of MM,①this experiment will detect levels of serum IL-17in patients with multiple myeloma, and then analyzed the relationship of the serum IL-17and MM activity/stability、the serum IL-17and MM stage、the serum IL-17and serum β2-microglobulin, in order to explore the clinical significance of IL-17in MM progression and prognosis,②and also we will detect the bone marrow concentrations of IL-17in patients with multiple myeloma bone disease, and to investigate its clinical significance.Methods:The expression of serum IL-17and β2-microglobulin in patients with multiple myeloma:①double antibody sandwich ELISA method was used to detect expression of serum IL-17from patients with multiple myeloma;②radioimmunoassay to detect the expression levels of multiple myeloma patients serum β2-microglobulin (β2-MG).The expression of bone marrow IL-17and bone marrow mononuclear cells’ RANKL mRNA from patients with multiple myeloma bone disease:①double antibody sandwich ELISA method was used to detect expression of bone marrow IL-17②RT-PCR was used to detect the RANKL mRNA expression from bone marrow mononuclear cells.Results:The expression of serum IL-17and β2-microglobulin from patients with multiple myeloma:①the serum concentrations of IL-17and β2-microglobulin from patients with multiple myeloma were significantly higher than those in the control group (p<0.05).②the serum concentrations of IL-17and β2-microglobulin in active stage were significantly higher than those in stable stage (p<0.05).③the serum concentrations of IL-17and β2-microglobulin were significantly elevated in stage III vs stages Ⅱ according to International Staging System (ISS)(p <0.05).④the serum IL-17and β2-microglobulin were significantly correlated (r=0.690, P <0.05).The expression of bone marrow IL-17and bone marrow mononuclear cells’ RANKL mRNA from patients with multiple myeloma bone disease:①in bone marrow supernatant, IL-17are expressed in both MM with bone disease group and control group, and both groups’ bone marrow mononuclear cells expressed RANKL mRNA.②IL-17and RANKL mRNA levels in bone marrow of patients with multiple myeloma bone disease were significantly higher than those in the control group (p<0.05).③the bone marrow concentrations of IL-17and bone marrow mononuclear cells’ RANKL mRNA expression in active stage were significantly higher than those in stable stage (p<0.05).④the bone marrow IL-17and RANKL were significantly correlated (r=0.690, p<0.05).Conclusion:IL-17may play an important role in the pathogenesis of multiple myeloma. |
