MRC National Institute for Medical Research, London
Science for Health
Hepcidin’s role in malaria
08 February 2013
Scientists at NIMR and in Nigeria have found that hepcidin levels are lower in cases of severe malaria. The research was published in Blood.
Cerebral malaria (CM) and severe malarial anemia (SMA) are the most serious life-threatening clinical syndromes of Plasmodium falciparum infection in childhood. Therefore it is important to understand the pathology underlying the development of CM and SMA. Although the physiopathologies of both severe syndromes have been widely investigated, the exact molecular and cellular events leading to severe childhood malaria cases have not completely been explained.
Human host response studies have suggested that an imbalance between pro- and anti-inflammatory cytokines could play a role in the establishment of severe malaria syndromes. Hepcidin is a peptide derived from a pre-pro-hormone produced in hepatocytes. Increased levels of hepcidin have been associated with UM but its level and role in severe malaria disease remains to be investigated.
Hepcidin has been linked to inflammation, iron-regulatory processes and anemia. Delmiro Fernadez-Reyes (pictured) in NIMR's Division of Parasitology, together with his collaborators in Nigeria, hypothesized that its function could explain differences between severe and mild cases of malaria. They studied hepcidin levels in cerebral malaria pediatric patients. Plasma and clinical data were obtained as part of a prospective case-control study of severe childhood malaria at the main tertiary hospital of the city of Ibadan, Nigeria.
They found that hepcidin levels are lower in children with SMA or with CM than those with milder outcome. Whilst different profiles of pro- and anti-inflammatory cytokines were observed between the malaria syndromes, circulatory hepcidin levels remained associated with the levels of its regulatory cytokine IL-6 and of the anti-inflammatory cytokine IL-10, irrespective of the iron status, anaemic status and of the general acute phase response. They propose a role for hepcidin in anti-inflammatory processes in childhood malaria.
Our study suggests that hepcidin has a particular role in the host response to malaria infection alongside IL-6 and IL-10 anti-inflammatory cytokines. The present study not only emphasizes the role of iron-regulatory and pro- and anti-inflammatory mechanisms in the establishment of the different severe syndromes but also supports the hypothesis that iron supplementation might not be required in the management of severe malaria. Also, hepcidin, although not a component of anemic status in the present study, could potentially be used to predict disease severity.
Delmiro Fernandez-Reyes
Original article
Florence Burté, Ph.D., Biobele J. Brown, Adebola E. Orimadegun, Wasiu A. Ajetunmobi, Nathaniel K. Afolabi, Francis Akinkunmi, Olayinka Kowobari, Samuel Omokhodion, Kikelomo Osinusi, Felix O. Akinbami, Wuraola A. Shokunbi, Olugbemiro Sodeinde, Delmiro Fernandez-Reyes (2013)
Circulatory hepcidin is associated with the anti-inflammatory response but not with iron or anemic status in childhood malaria
Blood Epub ahead of print. AbstractNews categories
© MRC National Institute for Medical Research
The Ridgeway, Mill Hill, London NW7 1AA
Top of page