Plasma cytokine levels in young and elderly twins: genes versus environment and relation to in vivo insulin action.
OBJECTIVE
We studied the impact of genetic versus pre- and postnatal environmental factors on the plasma levels of IL6, TNF and the soluble TNF receptor superfamily, member 1A (TNFRSF1A, previously known as TNF receptor type1 [TNFR1]).


METHODS
Using the hyperinsulinaemic-euglycaemic clamp, we assessed the association between cytokine levels and both peripheral insulin sensitivity and hepatic glucose production. Fasting plasma IL6, TNF and soluble TNFRSF1A levels were measured using ELISA in 55 young and 43 elderly twin pairs.


RESULTS
Plasma IL6 and TNF were influenced by genetic factors in young and elderly twins respectively, while no significant impact of genetics was found for soluble TNFRSF1A. Significant intra-twin pair correlations between birthweight and both IL6 and soluble TNFRSF1A levels were found. In addition to the effect of birthweight on IL6, age and fat % also significantly influenced IL6 levels, whereas soluble TNFRSF1A levels were significantly influenced by zygosity, age, fat % and sex. Plasma soluble TNFRSF1A was associated with higher plasma NEFA and to some extent with reduced insulin sensitivity. Plasma IL6 was associated positively with basal NEFA. TNF level was not associated with in vivo glucose or fat metabolism after correction for known confounders.


CONCLUSIONS
Plasma IL6 and soluble TNFRSF1A are influenced by the intrauterine environment. We found some evidence of a genetic component for TNF and IL6 in young and elderly twins respectively. Plasma IL6 may influence basal lipolysis, but neither plasma TNF nor IL6 levels are independently associated with hepatic or peripheral insulin action. Nevertheless, plasma soluble TNFRSF1A may play some role in the control of insulin action.
Grunnet
L
L
Steno Diabetes Centre, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark. loug@steno.dk
Poulsen
P
P
Klarlund Pedersen
B
B
Mandrup-Poulsen
T
T
Vaag
A
A
D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood* / Q000235:genetics; D001724:Birth Weight; D004797:Enzyme-Linked Immunosorbent Assay; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000502:physiology*; D007333:Insulin Resistance / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood* / Q000235:genetics; D012727:Sex Characteristics; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000235:genetics; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D015850:Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose