Interleukin 1 receptor antagonist is associated with changes in body composition during physiological GH substitution in patients with adult-onset growth hormone deficiency

Abstract

We examined the effect of GH substitution on adipose tissue-derived hormones and cytokines and sought to identify predictors for changes in body composition during therapy. Long-standing adult-onset GH deficiency (AO-GHD) is associated with increased body fat mass (FM) which, through production of hormones and inflammatory cytokines from adipose tissue, may contribute to different manifestations of the metabolic syndrome. Fifty-five patients with AO-GHD (24 women, 31 men, mean age 49 years) were enrolled in a placebo-controlled, double-blind crossover study. GH therapy was individually dosed to obtain an IGF-I concentration within the normal range for age and sex. GH and placebo were administered for 9 months each, separated by a 4-month washout period. Adipose tissue-derived cytokines were measured by enzyme immunoassay. GH treatment was associated with a significant decrease in IL-1 receptor antagonist (IL-1Ra) compared to placebo, which correlated with declining body FM (truncal and total) after GH substitution. The change in IL-1Ra was the strongest predictor of the variation in BFM in regression models. No changes were observed for leptin, adiponectin, soluble TNF receptor 1 or interleukin (IL)-8. The data indicate a possible unrecognized association between IL-1Ra and changes in body composition during GH substitution and suggest further research on the interaction between the GH-IGF axis and the IL-1 system.