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Malaria Journal
Published in: Malaria Journal 1/2012

Open Access 01-12-2012 | Research

Insights into deregulated TNF and IL-10 production in malaria: implications for understanding severe malarial anaemia

Authors: Philippe S Boeuf, Séverine Loizon, Gordon A Awandare, John KA Tetteh, Michael M Addae, George O Adjei, Bamenla Goka, Jørgen AL Kurtzhals, Odile Puijalon, Lars Hviid, Bartholomew D Akanmori, Charlotte Behr

Published in: Malaria Journal | Issue 1/2012

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Abstract

Background

Severe malarial anaemia (SMA) is a major life-threatening complication of paediatric malaria. Protracted production of pro-inflammatory cytokines promoting erythrophagocytosis and depressing erythropoiesis is thought to play an important role in SMA, which is characterized by a high TNF/IL-10 ratio. Whether this TNF/IL-10 imbalance results from an intrinsic incapacity of SMA patients to produce IL-10 or from an IL-10 unresponsiveness to infection is unknown. Monocytes and T cells are recognized as the main sources of TNF and IL-10 in vivo, but little is known about the activation status of those cells in SMA patients.

Methods

The IL-10 and TNF production capacity and the activation phenotype of monocytes and T cells were compared in samples collected from 332 Ghanaian children with non-overlapping SMA (n = 108), cerebral malaria (CM) (n = 144) or uncomplicated malaria (UM) (n = 80) syndromes. Activation status of monocytes and T cells was ascertained by measuring HLA-DR+ and/or CD69+ surface expression by flow cytometry. The TNF and IL-10 production was assessed in a whole-blood assay after or not stimulation with lipopolysaccharide (LPS) or phytohaemaglutinin (PHA) used as surrogate of unspecific monocyte and T cell stimulant. The number of circulating pigmented monocytes was also determined.

Results

Monocytes and T cells from SMA and CM patients showed similar activation profiles with a comparable decreased HLA-DR expression on monocytes and increased frequency of CD69+ and HLA-DR+ T cells. In contrast, the acute-phase IL-10 production was markedly decreased in SMA compared to CM (P = .003) and UM (P = .004). Although in SMA the IL-10 response to LPS-stimulation was larger in amplitude than in CM (P = .0082), the absolute levels of IL-10 reached were lower (P = .013). Both the amplitude and levels of TNF produced in response to LPS-stimulation were larger in SMA than CM (P = .019). In response to PHA-stimulation, absolute levels of IL-10 produced in SMA were lower than in CM (P = .005) contrasting with TNF levels, which were higher (P = .001).

Conclusions

These data reveal that SMA patients have the potential to mount efficient IL-10 responses and that the TNF/IL-10 imbalance may reflect a specific monocyte and T cell programming/polarization pattern in response to infection.
Appendix
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Metadata
Title
Insights into deregulated TNF and IL-10 production in malaria: implications for understanding severe malarial anaemia
Authors
Philippe S Boeuf
Séverine Loizon
Gordon A Awandare
John KA Tetteh
Michael M Addae
George O Adjei
Bamenla Goka
Jørgen AL Kurtzhals
Odile Puijalon
Lars Hviid
Bartholomew D Akanmori
Charlotte Behr
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2012
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-11-253

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