Context: Interleukin-2 (IL-2), a proinflammatory cytokine, has been used to treat malignancies. Increased cortisol and adrenocorticotropin (ACTH) were noted, but growth hormone (GH) secretion was... Show moreContext: Interleukin-2 (IL-2), a proinflammatory cytokine, has been used to treat malignancies. Increased cortisol and adrenocorticotropin (ACTH) were noted, but growth hormone (GH) secretion was not investigated in detail.Objective: We quantified GH secretion after a single subcutaneous injection of IL-2 in 17 young and 18 older healthy men in relation to dose, age, and body composition.Methods: This was a placebo-controlled, blinded, prospectively randomized, crossover study. At 20:00 hours IL-2 (3 or 6 million units/m(2)) or saline was injected subcutaneously. Lights were off between 23:00 and 07:00 hours. Blood was sampled at 10-minute intervals for 24 hours. Outcome measures included convolution analysis of GH secretion.Results: GH profiles were pulsatile under both experimental conditions and lower in older than young volunteers. Since the effect of IL-2 might be time limited, GH analyses were performed on the complete 24-hour series and the 6 hours after IL-2 administration. Total and pulsatile 24-hour GH secretion decreased nonsignificantly. Pulsatile secretion fell over the first 6 hours after IL-2 (P=.03), with visceral fat as a covariate (P=.003), but not age (P=.10). Plots of cumulative 2-hour bins of GH pulse mass showed a distinction by treatment and age groups: A temporary GH decrease of 32% and 28% occurred in the first 2-hour bins after midnight (P=.02 and .04) in young participants, whereas in older individuals no differences were present at any time point.Conclusion: This study demonstrates that IL-2 temporarily diminishes GH secretion in young, but not older, men. Show less
Background: Interleukin-2 (IL-2), one of the proinflammatory cytokines, is used in the treatment of certain malignancies. In some studies, transient increases in cortisol and ACTH secretion... Show moreBackground: Interleukin-2 (IL-2), one of the proinflammatory cytokines, is used in the treatment of certain malignancies. In some studies, transient increases in cortisol and ACTH secretion occurred. Thus, this agent may be used as an experimental probe of adrenal cortisol secretion.Objective: This study quantifies the effects of low and moderate doses of IL-2 on cortisol secretion and assesses the modulation by age, dose and body composition.Site: Mayo Clinical Translational Research Unit.Subjects: Study comprised 35 healthy men, 17 young and 18 older.Methods: Randomized prospective double-blind saline-controlled study of IL-2 administration in two doses with concurrent 10-min blood sampling for 24 h.Outcome measures: Deconvolution analysis and approximate entropy of cortisol secretion.Results: Low-dose IL-2 administration increased nocturnal pulsatile cortisol secretion from 1460 +/- 160 to 2120 +/- 220 nmol/L/8 h in young subjects and from 1680 +/- 105 to 1960 +/- 125 nmol/L/8 h (treatment P < 0.0001, but more in young than older, P = 0.02). Comparable results were obtained for total cortisol secretion (P treatment <0.0001, age effect P = 0.005). The higher IL-2 dose caused a large increase in young (P < 0.0001), but not in older (P = 0.90) subjects. This dose also increased approximate entropy from 0.877 +/- 0.041 to 1.024 +/- 0.049 (P = 0.008), pointing to reduced secretory orderliness. Incremental cortisol (nocturnal) secretion correlated negatively with visceral fat mass (R = -0.41, P = 0.019).Conclusion: In healthy men, IL-2 injection drives pulsatile cortisol secretion in a dose-dependent way in young, but not older, individuals and erodes cortisol secretory orderliness at a higher dose in young subjects. Cortisol responses are diminished with increasing abdominal visceral fat mass. Show less
