Genetic variation in IL-10 is associated with atopic reactivity in Gabonese schoolchildren

Biggelaar, Anita H. J. van den; Hua, T D; Rodrigues, Laura C.; Kremsner, Peter G.; Yazdanbakhsh, Maria; Kube, Dieter

doi:10.1016/j.jaci.2007.06.044

Cited by 7 publications

(6 citation statements)

References 9 publications

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“…Unlike previous reports, T cells stimulated with Con A (Figure 2) had higher levels of IL-10 production when obtained from individuals with the A allele and B cells stimulated with anti-IgM displayed the same trend (Figure 3). Our results are consistent with a recent report that showed peripheral blood mononuclear cells stimulated with phytohemagglutinin, from individuals homozygous for the A allele at position -571, produced higher levels of IL-10 than individuals homozygous for the C allele, though in their study there was additional contribution to IL-10 production from other SNPs on the IL-10 promoter [37]. Some of these differences in comparison to the other reports may reflect individual variability in representation of distinct mononuclear cell populations amongst PBMCs.…”

Section: Discussionsupporting

confidence: 93%

Differential interleukin-10 production stratified by −571 promoter polymorphism in purified human immune cells

Steinke¹,

Barekzi²,

Huyett³

et al. 2007

Cellular Immunology

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SummaryA C-to-A base substitution has been identified at bp -571 in the IL-10 promoter and has been linked to numerous diseases. To investigate the role of this polymorphism on IL-10 production, T cells, B cells and monocytes were enriched from peripheral blood from subjects either homozygous for the C or A allele. Treatment of monocytes and B cells with lipopolysaccharide from individuals homozygous for the C allele resulted in higher levels of IL-10 production as compared to monocytes from individuals homozygous for the A allele. Though not statistically significant, when B cells were treated with anti-IgM or T cells with concanavalin A higher levels of IL-10 were produced from individuals homozygous for the A allele. Changes in IL-10 protein production were paralleled by similar changes in IL-10 mRNA production. These results demonstrate that changes in IL-10 production observed due to the -571 genotype depend on both cell type and stimulus.

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Section: Discussionsupporting

confidence: 93%

Differential interleukin-10 production stratified by −571 promoter polymorphism in purified human immune cells

Steinke¹,

Barekzi²,

Huyett³

et al. 2007

Cellular Immunology

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“…Similarly, the IL13‐1055T allele has been associated with both low schistosome burden in Mali and an increased asthma risk in Europe [108, 109], and the ADRB2 Gly16 allele has been associated with low Ascaris burden in Venezuela and more severe asthma [110, 111]. Helminth‐mediated immuno‐modulation may also be affected by host genetics, as IL‐10 polymorphisms have been associated with SPT positivity and IL‐10 production in children in Gabon [112].…”

Section: Does Atopy Protect Against Helminth Infection? Reverse Causamentioning

confidence: 99%

Do helminth parasites protect against atopy and allergic disease?

Flohr¹,

Quinnell²,

Britton³

2009

Clin Experimental Allergy

175

144

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Allergic diseases are rare in areas with high helminth parasite exposure and common where helminth exposure is lacking or significantly reduced, such as urban areas of developing countries and industrialized nations. Studies suggest that helminths induce a systemic immuno-modulatory network, including regulatory T cells and anti-inflammatory IL-10, which might play a key role in the protection against the allergic phenotype. Here, we review the current cross-sectional, birth cohort, and intervention study evidence for a protective effect of helminth infection on allergy. There is increasing evidence for a causal relationship between helminth infection and reduced skin prick test responsiveness to allergens. Cross-sectional studies have shown a consistent negative relationship, and these results have been confirmed in several, although not all, intervention studies. The immunological basis for this protective effect is less clear. Recent studies do not support the mast-cell IgE saturation hypothesis, but suggest that protection is associated with IL-10 production. As for allergic disease, cross-sectional studies support a negative relationship between clinical asthma and infection with some helminth species, particularly hookworm, but more studies are required to draw conclusions for eczema and rhinitis. In addition, none of the few intervention studies to date have demonstrated an increase in clinical allergy after helminth treatment, and further studies are needed. Furthermore, we are only beginning to understand the host genetic factors that are potentially involved. A genetically predetermined T-helper type 2 cell-dominated cytokine milieu reduces parasite burden and may enhance host survival in an environment where helminth parasites are prevalent. Lack of parasite exposure in such hosts might lead to hypersensitivity to seemingly minor environmental allergen stimuli. Large birth cohort studies in helminth-endemic areas that use epidemiological, genetic, and immunological tools are required to further examine how helminth parasites affect the development of atopy and allergic disease. Intervention studies with hookworm in parasite-naïve allergic individuals are currently ongoing in the United Kingdom to test the above hypotheses further.

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“…32 Furthermore, it might also lead to initiation and amplification of Th2 responses. 15 Arimitsu et al 33 confirmed the higher production of IL-18 by monocytes with the −137 GG genotype. The authors indicated that the −137 G allele contributed to the higher tendency to produce increased amount of IL-18; they also suggested its reflection on allergic disease phenotypes.…”

Section: Discussionmentioning

confidence: 94%