losartan-potassium and Castleman-Disease

Dysregulated production of hepcidin is implicated in anemia of inflammation, whereas interleukin-6 (IL-6) is a major inducer of hepcidin production. Overproduction of IL-6 is responsible for pathogenesis of multicentric Castleman disease (MCD), a rare lymphoproliferative disorder accompanied by systemic inflammatory responses and anemia. In this study, we investigated the roles of hepcidin and IL-6 in anemia of inflammation and the long-term effects of anti-IL-6 receptor antibody (tocilizumab) treatment on serum hepcidin and iron-related parameters in MCD patients. We found that tocilizumab treatment resulted in a rapid reduction of serum hepcidin-25 in 5 of 6 MCD patients. Long-term reductions, accompanied by progressive normalization of iron-related parameters and symptom improvement, were observed in 9 of 9 cases 1.5, 3, 6, and 12 months after the start of tocilizumab treatment. In in vitro experiments, IL-6-induced up-regulation of hepcidin mRNA in hepatoma cell lines was completely inhibited by tocilizumab but increased in the presence of patients' sera. Our results suggest that, although multiple factors affect serum hepcidin levels, IL-6 plays an essential role in the induction of hepcidin in MCD. This accounts for the long-term ameliorative effect of IL-6 blockage with tocilizumab on anemia by inhibiting hepcidin production in MCD patients.

Topics: Anemia; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antimicrobial Cationic Peptides; Castleman Disease; Cell Line; Down-Regulation; Erythropoietin; Hepatocytes; Hepcidins; Humans; Inflammation; Interleukin-6; Iron; Receptors, Interleukin-6

Severe anemia A 37 year-old male with therapy resistant multicentric Castleman's disease (MCD) anemia was treated by subcutaneous injection of erythropoietin. Although immunoglobulin and CRP concentration increased, anemia obviously improved with hemoglobin levels increasing from 4.8 g/dl to 8.5 g/dl without any side effects. Colony assay revealed that the bone marrow mononuclear cells responded to erythropoietin in a dose dependent manner. The mechanism of anemia of MCD is not clearly understood, and treatment is sometimes very difficult. There is no other previous report concerning erythropoietin as a treatment for anemia in MCD.

Topics: Adult; Anemia; Castleman Disease; Erythroid Precursor Cells; Erythropoietin; Humans; Injections, Subcutaneous; Male

Topics: Adult; Anemia; Castleman Disease; Drug Resistance; Erythropoietin; Female; Humans; Thrombocytosis

Topics: Autoantibodies; Blood Viscosity; Castleman Disease; Child; Erythropoietin; Humans; Male; Syndrome