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Abstract
Recently, it has been shown that the capacity of the innate immune system to produce cytokines relates to skeletal muscle mass and strength in older persons. The interleukin-10 (IL-10) gene regulates the production capacities of IL-10 and tumour necrosis factor-α (TNF-α). In rural Ghana, IL-10 gene variants associated with different production capacities of IL-10 and TNF-α are enriched compared with Caucasian populations. In this setting, we explored the association between these gene variants and muscle strength. Among 554 Ghanaians aged 50 years and older, we determined 20 single nucleotide polymorphisms in the IL-10 gene, production capacities of IL-10 and TNF-α in whole blood upon stimulation with lipopolysaccharide (LPS) and handgrip strength as a proxy for skeletal muscle strength. We distinguished pro-inflammatory haplotypes associated with low IL-10 production capacity and anti-inflammatory haplotypes with high IL-10 production capacity. We found that distinct haplotypes of the IL-10 gene associated with handgrip strength. A pro-inflammatory haplotype with a population frequency of 43.2% was associated with higher handgrip strength (P = 0.015). An anti-inflammatory haplotype with a population frequency of 7.9% was associated with lower handgrip strength (P = 0.006). In conclusion, variants of the IL-10 gene contributing to a pro-inflammatory cytokine response associate with higher muscle strength, whereas those with anti-inflammatory response associate with lower muscle strength. Future research needs to elucidate whether these effects of variation in the IL-10 gene are exerted directly through its role in the repair of muscle tissue or indirectly through its role in the defence against infectious diseases.
Highlights
Interleukin-10 (IL-10) is an anti-inflammatory cytokine with important regulatory effects on inflammatory responses
These variants have functional significance: some are related to a pro-inflammatory cytokine production capacity, with lower IL-10 and higher tumour necrosis factor a (TNF-a) levels upon whole-blood stimulation with LPS, while others are related to an inverse anti-inflammatory response (Kuningas et al, 2009; May et al, 2009b; Boef et al, 2012)
Their characteristics were similar as compared with all 4336 individuals of whom IL-10 gene variants were measured and with all 923 individuals of whom handgrip strength was measured
Summary
Interleukin-10 (IL-10) is an anti-inflammatory cytokine with important regulatory effects on inflammatory responses. We have earlier reported that specific IL-10 gene variants are enriched in Ghanaian elderly living under adverse conditions (Kuningas et al, 2009) These variants have functional significance: some are related to a pro-inflammatory cytokine production capacity, with lower IL-10 and higher TNF-a levels upon whole-blood stimulation with LPS, while others are related to an inverse anti-inflammatory response (Kuningas et al, 2009; May et al, 2009b; Boef et al, 2012). The functional variation in the genetic determinants of cytokine production capacity forms a meaningful instrument to study the effects of different cytokine production capacities largely free from confounding and reverse causality (Davey Smith & Ebrahim, 2003)
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