Interleukin-10 Regulates Hepcidin in Plasmodium falciparum Malaria

Honglei Huang,Ehab Moussa,Abhinay Ramaprasad,Matthew S Alkaitis,Abigail A Lamikanra,Climent Casals-Pascual,Marie L Thézénas,David J Roberts,Alister G Craig

doi:10.1371/journal.pone.0088408

Abstract

BackgroundAcute 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.MethodsWe 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.FindingsWe 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.ConclusionIL-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.

Highlights

Anaemia remains a global public health problem world-wide that affects mainly young children and pregnant women [1,2]
IL-10 can directly regulate hepcidin in primary macrophages but not in HepG2 cells
Previous observations have suggested that Plasmodium falciparuminfected erythrocytes (IE) or their products could directly or indirectly induce hepcidin secretion from peripheral blood mononuclear cells (PBMCs)

Summary

Introduction

Anaemia remains a global public health problem world-wide that affects mainly young children and pregnant women [1,2]. It is clear that hepcidin, the major inhibitor of iron absorption and availability, is raised during acute and asymptomatic parasitemia and during infection [3,5,6,7]. Macrophages store and supply iron to erythroblasts in the bone marrow This is critical for the development of new red blood cells and failure to provide iron to developing erythroid cells will inevitably result in anaemia [8]. This process is tightly regulated by the liver-produced hormone hepcidin, the master regulator of iron homeostasis. 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

Results

Conclusion