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.
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.
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.
Citation: Huang H, Lamikanra AA, Alkaitis MS, Thézénas ML, Ramaprasad A, et al. (2014) Interleukin-10 Regulates Hepcidin in Plasmodium falciparum Malaria. PLoS ONE 9(2): e88408. doi:10.1371/journal.pone.0088408
Editor: Alister G. Craig, Liverpool School of Tropical Medicine, United Kingdom
Received: November 12, 2013; Accepted: January 6, 2014; Published: February 10, 2014
Copyright: © 2014 Huang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: CC-P is supported by the Medical research Council (Clinician Scientist Fellowship: G0701885). DJR is supported by the National Blood Service, and the National Institute for Health Research. The research was carried out at the Wellcome Trust Centre for Human Genetics (Oxford, UK) [077383/Z/05/Z], and the National Health Service Blood and Transplant – Oxford Centre. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Read Full Article: interleukin-10-hipcidin-malaria-plos (PDF)