The role of hepcidin in the pathogenesis of multiple myeloma related anemia and the value of hepcidin in clinical follow-up

Introduction: Anemia is an important cause of morbidity and mortality in multiple myeloma (MM). It may be the first presenting sign in 80% of the MM patients. Hepsidin, produced in the liver where its production is induced by IL-6, is an acute phase reactant which has a central role in the chronic disease anemia. Hepsidin causes anemia by means of preventing iron from the intestines and secretion from the macrophages. Serum cytokine levels increase in MM as in many other malign hematologic malignancies. IL-6 level increases in MM. Increased cytokines and acute phase reactants have important roles in the anemia seen in MM. However, the etiopathogenesis of the anemia in MM is still unclear. Thus, we researched the role of the hepsidin in the anemia seen in MM, its relation with the cytokines and its role in disease activity.Materials and Methods: 29 recently diagnosed MM patients were included in the study. Serum levels of hepsidin, TNF-?, IL-6 and the hematologic parameters having prognostic value (ß2 microglobulin, CRP, LDH ve ESR) were measured. 6 patients died during the therapy, so the same parameters were measured for the remaining 23 patients after 3-4 cyles of chemotherapy. The results were compared with the results of 25 healthy controls.Results: The post-treatment serum levels of hepsidin and IL-6 were significiantly decreased ( respectively, p=0.008 and p=0.021 ). However, the post-treatment levels were significantly high as compared to the control group. We didnot find a significant difference between the pre and post-treatment levels of TNF-? and not find a significant difference in between group analysis as compared to control group . Significant increase was found in post-treatment hemoglobin (Hb) ( p= 0.043). Pre and post- treatment levels of the hepsidin and IL-6 were significantly and positively correlated. Pre- treatment levels of the Hb and the hepsidin were significantly and negatively correlated; however, after the treatment this correlation disappeared. There were no correlations between the serum levels of hepsidin and the known prognostic parameters for MM including LDH, ß2 microglobulin and CRP. No significant correlations were found among the serum hepsidin levels of the MM sub-types and these subtypes? the bone marrow plasma cell ratio index.Conlusion: There is a significant correlation between the increased serum IL-6 and the hepsidin levels. IL-6 and hepsidin levels decrease as inflamation diminishes. Hepsidin seems to have a direct role or act a mediator in the pathogenesis of anemia seen in MM. There were no associations between the serum hepsidin level and the levels of the known prognostic parameters of MM including LDH, CRP and ß2 microglobulin. However, because of the close relation of hepsidin with the other prognostic factors, both Hb and IL-6, it may be considered to be used in patient follow-up in MM patients. Besides, hepsidin might be speculated to be used as an acute phase reactant.Key Words: Multiple Myeloma, Serum Hepsidin, TNF-?, IL-6 level