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doi:10.1016/j.clim.2007.08.007 
Copyright © 2007 Elsevier Inc. All rights reserved.
Increased circulating interleukin (IL)-23 in children with malarial anemia: In vivo and in vitro relationship with co-regulatory cytokines IL-12 and IL-10
John M. Ong’echaa, b, 
, 
, Allison M. Remob, Jan Kristoffb, James B. Hittnerc, Tom Werea, Collins Oumaa, Richard O. Otienoa, John M. Vululed, Christopher C. Kellerb, e, Gordon A. Awandareb and Douglas J. Perkinsa, b
Received 5 July 2007;
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Abstract
Severe malarial anemia (SMA) is a leading cause of mortality among children in sub-Saharan Africa. Although the novel cytokine, interleukin (IL)-23, promotes anemia in chronic inflammatory diseases, the role of IL-23 in SMA remains undefined. Since IL-23 and IL-12 share the IL-12p40 subunit and IL-12Rβ1 receptor, and are down-regulated by IL-10, relationships among these cytokines were explored in Kenyan children with varying severities of malarial anemia. Children with malarial anemia had increased circulating IL-23 and IL-10 and decreased IL-12 relative to healthy controls. Enhanced anemia severity and elevated parasitemia were associated with increased IL-10 relative to IL-23 and IL-12. Further exploration of the relationships among the cytokines using an in vitro model in which peripheral blood mononuclear cells were treated with synthetic hemozoin (sHz, malarial pigment) revealed that IL-12p35 and IL-23p19 transcripts had a sustained induction over 72 h, while IL-12p40 and IL-10 message peaked at 24 h, and rapidly declined thereafter. Taken together, results here show that IL-23 is elevated in children with malarial anemia, and that IL-10 and IL-12 appear to have important regulatory effects on IL-23 production during childhood malaria.
Keywords: Plasmodium falciparum; Malarial anemia; Hemozoin; Cytokines; IL-23; IL-12; IL-10
Article Outline
- Introduction
- Materials and methods
- Study area
- Study population
- Hemoglobin measurements
- Parasitemia determination
- Circulating cytokine measurements
- PBMC isolation and culture
- sHz preparation
- RNA isolation
- Quantitative real-time RT-PCR
- Statistical analyses
- Results
- Characteristics of the study participants
- Absolute cytokine levels and cytokine ratios in the clinical groups
- Relationship between absolute cytokine levels, cytokine ratios, and parasitemia
- Association between absolute cytokine levels, cytokine ratios, and anemia
- Effect of sHz on PBMC cytokine gene expression
- Discussion
- Acknowledgements
- References
