Children with familial hypercholesterolemia are characterized by an inflammatory imbalance between the tumor necrosis factor α system and interleukin-10.
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.
Department of Nutrition, Institute for Basic Medical Sciences, University of Oslo, Blindern, 0316 Oslo, Norway.
Ingunn
I
Narverud
Thor
T
Ueland
Marit S
MS
Nenseter
Kjetil
K
Retterstøl
Vibeke H
VH
Telle-Hansen
Bente
B
Halvorsen
Leiv
L
Ose
Pål
P
Aukrust
Kirsten B
KB
Holven
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation; D016753:Interleukin-10 / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000235:genetics
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10