Interleukin-10 (IL-10) Polymorphisms Are Associated with IL-10 Production and Clinical Malaria in Young Children

ABSTRACT The role of interleukin-10 (IL-10) in malaria remains poorly characterized. The aims of this study were to investigate (i) whether genetic variants of the IL-10 gene influence IL-10 production and (ii) whether IL-10 production as well as the genotypes and haplotypes of the IL-10 gene in young children and their mothers are associated with the incidence of clinical malaria in young children. We genotyped three IL-10 single nucleotide polymorphisms in 240 children and their mothers from a longitudinal prospective cohort and assessed the IL-10 production by maternal peripheral blood mononuclear cells (PBMCs) and cord blood mononuclear cells (CBMCs). Clinical episodes of Plasmodium falciparum malaria in the children were documented until the second year of life. The polymorphism IL-10 A-1082G (GCC haplotype of three SNPs in IL-10) in children was associated with IL-10 production levels by CBMC cultured with P. falciparum-infected erythrocytes (P = 0.043), with the G allele linked to low IL-10 production capacity. The G allele in children was also significantly associated with a decreased risk for clinical malaria infection in their second year of life (P = 0.016). Furthermore, IL-10 levels measured in maternal PBMCs cultured with infected erythrocytes were associated with increased risk of malaria infection in young children (P < 0.001). In conclusion, IL-10 polymorphisms and IL-10 production capacity were associated with clinical malaria infections in young children. High IL-10 production capacity inherited from parents may diminish immunological protection against P. falciparum infection, thereby being a risk for increased malaria morbidity.

[1]  Q. Bassat,et al.  The Role of Age and Exposure to Plasmodium falciparum in the Rate of Acquisition of Naturally Acquired Immunity: A Randomized Controlled Trial , 2012, PloS one.

[2]  B. Świątek.  Is interleukin-10 gene polymorphism a predictive marker in HCV infection? , 2012, Cytokine & growth factor reviews.

[3]  Weihong Zhao,et al.  Relationships between tumour necrosis factor‐α, interleukin‐12B and interleukin‐10 gene polymorphisms and hepatitis B in Chinese Han haemodialysis patients , 2012, Nephrology.

[4]  M. Goldman,et al.  Interleukin-10 , 2012, BioDrugs.

[5]  Xiaodong Wu,et al.  Association of IL-10−1082 G/G genotype with lower mortality of acute respiratory distress syndrome in a Chinese population , 2011, Molecular Biology Reports.

[6]  M. Póvoa,et al.  Increased interleukin-10 and interferon-γ levels in Plasmodium vivax malaria suggest a reciprocal regulation which is not altered by IL-10 gene promoter polymorphism , 2011, Malaria Journal.

[7]  P. Holt,et al.  Regulatory role of IL10 genetic variations in determining allergen-induced T(H)2 cytokine responses in children. , 2011, The Journal of allergy and clinical immunology.

[8]  P. Alonso,et al.  Comparison of commercial kits to measure cytokine responses to Plasmodium falciparum by multiplex microsphere suspension array technology , 2011, Malaria Journal.

[9]  Shunlai Sun,et al.  Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis B to interferon alfa , 2011, Virology Journal.

[10]  F. Pan,et al.  Interleukin-10 gene polymorphisms in association with susceptibility to chronic hepatitis C virus infection: a meta-analysis study , 2010, Archives of Virology.

[11]  F. Shuaib,et al.  Elevated Levels of IL-10 and G-CSF Associated with Asymptomatic Malaria in Pregnant Women , 2010, Infectious diseases in obstetrics and gynecology.

[12]  W. Zheng,et al.  Distinct host‐related dendritic cell responses during the early stage of Plasmodium yoelii infection in susceptible and resistant mice , 2010, Parasite immunology.

[13]  P. Slagboom,et al.  Polymorphisms in TLR4 and TLR2 genes, cytokine production and survival in rural Ghana , 2010, European Journal of Human Genetics.

[14]  R. Olomi,et al.  Alterations in early cytokine-mediated immune responses to Plasmodium falciparum infection in Tanzanian children with mineral element deficiencies: a cross-sectional survey , 2010, Malaria Journal.

[15]  J. Goldblatt,et al.  The era of genome-wide association studies: opportunities and challenges for asthma genetics , 2009, Journal of Human Genetics.

[16]  E. Vartiainen,et al.  Opposite gene by environment interactions in Karelia for CD14 and CC16 single nucleotide polymorphisms and allergy , 2009, Allergy.

[17]  Y. Ye,et al.  Combined effect of IL‐10 and TGF‐β1 promoter polymorphisms as a risk factor for aspirin‐intolerant asthma and rhinosinusitis , 2009, Allergy.

[18]  I. Baydar,et al.  TNF-α, TGF-β, IL-10, IL-6 and IFN-γ gene polymorphisms as risk factors for brucellosis , 2009 .

[19]  Liuda Ziaugra,et al.  SNP Genotyping Using the Sequenom MassARRAY iPLEX Platform , 2009, Current protocols in human genetics.

[20]  I. Baydar,et al.  TNF-alpha, TGF-beta, IL-10, IL-6 and IFN-gamma gene polymorphisms as risk factors for brucellosis. , 2009, The new microbiologica.

[21]  J. Goldblatt,et al.  Does the relationship between IgE and the CD14 gene depend on ethnicity? , 2008, Allergy.

[22]  J. Hittner,et al.  Haplotypes of IL-10 promoter variants are associated with susceptibility to severe malarial anemia and functional changes in IL-10 production , 2008, Human Genetics.

[23]  E. Riley,et al.  IL-10: The Master Regulator of Immunity to Infection , 2008, The Journal of Immunology.

[24]  N. Rezaei,et al.  IL-10, TGF-ß, IL-2, IL-12, and IFN-γ Cytokine Gene Polymorphisms in Asthma , 2008, The Journal of asthma : official journal of the Association for the Care of Asthma.

[25]  Jun Liu,et al.  Plasmodium yoelii: distinct CD4(+)CD25(+) regulatory T cell responses during the early stages of infection in susceptible and resistant mice. , 2007, Experimental parasitology.

[26]  J. Hittner,et al.  Acquisition of Hemozoin by Monocytes Down-Regulates Interleukin-12 p40 (IL-12p40) Transcripts and Circulating IL-12p70 through an IL-10-Dependent Mechanism: In Vivo and In Vitro Findings in Severe Malarial Anemia , 2006, Infection and Immunity.

[27]  Paul Scheet,et al.  A fast and flexible statistical model for large-scale population genotype data: applications to inferring missing genotypes and haplotypic phase. , 2006, American journal of human genetics.

[28]  D. Kwiatkowski,et al.  Analysis of IL10 haplotypic associations with severe malaria , 2005, Genes and Immunity.

[29]  Inacio Mandomando,et al.  Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial , 2004, The Lancet.

[30]  Z. Premji,et al.  Higher IL‐10 levels are associated with less effective clearance of Plasmodium falciparum parasites , 2004, Parasite immunology.

[31]  B. Lell,et al.  Plasma interleukin-10:Tumor necrosis factor (TNF)-alpha ratio is associated with TNF promoter variants and predicts malarial complications. , 2000, The Journal of infectious diseases.

[32]  Ching Li,et al.  A Defect in Interleukin-10 Leads to Enhanced Malarial Disease in Plasmodium chabaudi chabaudi Infection in Mice , 1999, Infection and Immunity.

[33]  B. Nahlen,et al.  A low interleukin-10 tumor necrosis factor-alpha ratio is associated with malaria anemia in children residing in a holoendemic malaria region in western Kenya. , 1999, The Journal of infectious diseases.

[34]  V. Adabayeri,et al.  Low plasma concentrations of interleukin 10 in severe malarial anaemia compared with cerebral and uncomplicated malaria , 1998, The Lancet.

[35]  M. Goldman,et al.  Interleukin‐10 modulates susceptibility in experimental cerebral malaria , 1997, Immunology.

[36]  M. Lazarus,et al.  An investigation of polymorphism in the interleukin-10 gene promoter. , 1997, European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics.