Inflammatory imbalance linked to atherosclerosis in FH children
MedWire News: An imbalance in inflammatory markers in children with familial hypercholesterolemia (FH) may contribute to accelerated atherogenesis, researchers report.
The findings, published in the journal Atherosclerosis, show that FH children are characterized by an inflammatory imbalance between tumor necrosis factor (TNF)α and the anti-inflammatory cytokine, interleukin (IL)-10.
Kirsten Holven (University of Oslo, Norway) and colleagues say that "the inflammatory cytokine TNFα has been regarded as a key mediator in the development of atherosclerosis." Their results therefore suggest that the imbalance observed in these individuals may contribute to an accelerated atherosclerotic process.
The researchers compared serum levels of TNFα, as well as soluble TNF receptors (sTNFRs), and IL-10 in clinically healthy children aged 7-20 years with (n=102) and without (n=48) heterozygous FH.
They also measured levels of these inflammatory and anti-inflammatory markers in adult FH patients (n=20) and healthy adult controls (n=16).
Analysis of their results showed that, compared with the control children, the FH group had higher TNFα serum levels (2.14 vs 1.43 ng/ml) accompanied by lower sTNFR2 levels (1.9 ng/ml vs 2.1 ng/ml). This led to a significantly increased ratio of TNFα to sTNFRs, potentially reflecting enhanced activity in the TNFα system.
In addition, FH children were observed to have significantly lower levels of IL-10 (0.74 vs 1.11 pg/ml), resulting in an increased ratio of TNFα to IL-10.
None of the parameters differed between adult FH patients and adult healthy controls, however.
Holven and team say that a "combination of raised levels of the inflammatory mediators (ie, TNFα) and decreased levels of the anti-inflammatory or resolving mediators (ie, IL-10) may be of importance for accelerated atherogenesis in FH children."
They add that the decreased levels of IL-10 and sTNFRs in FH children may "reflect an impaired interrelated anti-inflammatory potential in these individuals, contributing to a state of non-resolving inflammation in this early stage of atherogenesis."
The findings also suggest some differences between the inflammatory phenotype of FH children and adults, thereby implicating inflammation as an early characteristic of atherogenesis in pre-disposed individuals.
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By Nikki Withers