title: Erythropoietin administration suppresses human monocyte function in vitro and during therapy-induced anemia in HCV patients.
abstract: Erythropoietin (EPO) is a hormone that controls red blood cell production. Binding of EPO to the EPO-receptor results in increased numbers of red blood cells in the circulation, which makes EPO a potent molecule to treat anemia in various groups of patients. Although numerous studies have examined the clinical effects of EPO, its immunological effects have received less attention. In this study, we examined the immunological effects of EPO on human monocytes. We show that human monocytes express EPO receptor mRNA, and are responsive to EPO in cell culture. In vitro exposure of PBMC from individuals to EPO and the TLR4 ligand LPS showed a significant reduction of monocytes producing IL-6 and TNF, while the frequencies of IL-12p40, IL-10, MIP-1β and IL-8-producing cells did not change upon incubation with EPO. In addition, EPO did increase the phagocytic activity but did not affect the ability to produce ROS by monocytes. Moreover, we studied eight chronic HCV patients undergoing treatment with peg-IFN and ribavirin, who were administered EPO for treatment-induced anemia. Blood was collected before and 7 days after EPO injection. In 7 patients, we observed a significant decline at day 7 after EPO administration of the frequency of monocytes producing various pro-inflammatory cytokines following stimulation with the TLR4 ligand LPS and the TLR7/8 ligand R848, which is in line with our in vitro findings. Our findings demonstrate an inhibitory effect of EPO on the secretion of effector molecules by monocytes and a stimulatory effect on the phagocytic activity by monocytes.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, The Netherlands.
authors.forename: Michelle
authors.initials: M
authors.lastname: Spaan
authors.forename: Zwier M A
authors.initials: ZM
authors.lastname: Groothuismink
authors.forename: Ludi
authors.initials: L
authors.lastname: Koning
authors.forename: Robert
authors.initials: R
authors.lastname: Roomer
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: Robert J
authors.initials: RJ
authors.lastname: De Knegt
authors.forename: André
authors.initials: A
authors.lastname: Boonstra
mesh_terms: D000740:Anemia / Q000139:chemically induced* / Q000188:drug therapy; D004921:Erythropoietin / Q000008:administration & dosage* / Q000494:pharmacology; D004926:Escherichia coli / Q000378:metabolism; D016174:Hepacivirus / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism; D012254:Ribavirin / Q000009:adverse effects; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D008024:Ligands; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D017467:Receptors, Erythropoietin; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D004921:Erythropoietin; D012254:Ribavirin