Interleukin-2 drives cortisol secretion in an age-, dose-, and body composition-dependent way

Abstract

Background: Interleukin-2 (IL-2), one of the proinflammatory cytokines, is used in the treatment of certain malignancies. In some studies, transient i ncreases in cortisol and ACTH secretion occurred. Thus, this agent may be used as an exp erimental probe of adrenal cortisol secretion. Objective: This study quantifies the effects of low and moderate doses of I L-2 on cortisol secretion and assesses the modulation by age, dose and body com position. 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 sampli ng for 24 h. Outcome measures: Deconvolution analysis and approximate entropy of cortisol secretion. Results: Low-dose IL-2 administration increased nocturnal pulsatile cor tisol 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 secre tion in a dose-dependent way in young, but not older, individuals and erodes c ortisol secretory orderliness at a higher dose in young subjects. Cortisol respon ses are diminished with increasing abdominal visceral fat mass.

Keywords

• cytokines
• interleukin
• inflammation
• adrenal
• cortisol