Children with familial hypercholesterolemia are characterized by an inflammatory imbalance between the tumor necrosis factor α system and interleukin-10

Abstract

Objective: Familial hypercholesterolemia (FH) is associated with increased risk of premature atherosclerosis. Increasing evidence supports involvement of inflammation in atherogenesis. The inflammatory cytokine tumor necrosis factor (TNF)α has been regarded as a key mediator in the development of atherosclerosis due to its involvement in several stages in this process. We hypothesized that children with FH, as a model of early atherosclerosis, have different serum levels of inflammation markers than healthy control children.

Methods: We measured serum levels of TNFα, as well as its endogenous inhibitors (i.e., soluble TNF receptors [sTNFR] 1 and 2) and the anti-inflammatory cytokine interleukin (IL)-10 in healthy children (7-20 years) with (n=102) and without (n=48) heterozygote FH as well as adult FH subjects (n=20) and healthy adult controls (n=16).

Results: The main findings were: Compared to control children, FH children had higher serum levels of TNFα, accompanied by lower sTNFRs levels, resulting in an increased TNFα/sTNFRs ratio (P<0.05), potentially reflecting enhanced TNFα activity. In contrast to the increased TNFα levels, FH children had decreased serum levels of IL-10 (P<0.01) resulting in an increased TNFα/IL-10 ratio (P<0.01). We did not observe any difference in the same parameters between adult subjects with and without FH.

Conclusions: FH children are characterized by an inflammatory imbalance between TNFα and IL-10, potentially contributing to the accelerated atherosclerotic process in these individuals.