title: Interleukin-10 regulates hepcidin in Plasmodium falciparum malaria.
abstract: BACKGROUND
  Acute malarial anemia remains a major public health problem. Hepcidin, the major hormone controlling the availability of iron, is raised during acute and asymptomatic parasitemia. Understanding the role and mechanism of raised hepcidin and so reduced iron availability during infection is critical to establish evidence-based guidelines for management of malaria anemia. Our recent clinical evidence suggests a potential role of IL-10 in the regulation of hepcidin in patients with acute P. falciparum malaria.
  
  
  METHODS
  We have measured secretion of hepcidin by primary macrophages and the hepatoma cell line HepG2 stimulated with IL-10, IL-6 and Plasmodium falciparum-infected erythrocytes.
  
  
  RESULTS
  We have observed that IL-10 and IL-6 production increased in primary macrophages when these cells were co-cultured with Plasmodium falciparum-infected erythrocytes. We found that IL-10 induced hepcidin secretion in primary macrophages in a dose-dependent manner but not in HepG2 cells. These effects were mediated through signal transducer and activator of transcription (STAT) 3-phosphorylation and completely abrogated by a specific STAT3 inhibitor.
  
  
  CONCLUSIONS
  IL-10 can directly regulate hepcidin in primary macrophages but not in HepG2 cells. This effect can be modulated by Plasmodium falciparum. The results are consistent with a role for IL-10 in modulating iron metabolism during acute phase of infection.
authors: Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors: Honglei
authors: H
authors: Huang
authors: Nuffield Department of Clinical Laboratory Sciences, University of Oxford, and National Health Service Blood and Transplant, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
authors: Abigail A
authors: AA
authors: Lamikanra
authors: Nuffield Department of Clinical Laboratory Sciences, University of Oxford, and National Health Service Blood and Transplant, John Radcliffe Hospital, Headington, Oxford, United Kingdom ; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, United States of America.
authors: Matthew S
authors: MS
authors: Alkaitis
authors: Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors: Marie L
authors: ML
authors: Thézénas
authors: Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom ; King Abdullah University of Science and Technology, Saudi Arabia.
authors: Abhinay
authors: A
authors: Ramaprasad
authors: Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom ; King Abdullah University of Science and Technology, Saudi Arabia.
authors: Ehab
authors: E
authors: Moussa
authors: Nuffield Department of Clinical Laboratory Sciences, University of Oxford, and National Health Service Blood and Transplant, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
authors: David J
authors: DJ
authors: Roberts
authors: Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors: Climent
authors: C
authors: Casals-Pascual
mesh_terms: D002478:Cells, Cultured; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D056945:Hep G2 Cells; D064451:Hepcidins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism; D016778:Malaria, Falciparum / Q000378:metabolism* / Q000469:parasitology; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D064451:Hepcidins; D015850:Interleukin-6; D012333:RNA, Messenger; D016753:Interleukin-10