Growth Hormone Secretion Does Not Increase After Interleukin-2 Administration in Healthy Men

Abstract

Abstract Context: Interleukin-2 (IL2), a proinflammatory cytokine, is used for treatment of malignancies. Increased cortisol and ACTH were noted, but GH secretion was not investigated in detail. This is the first study in healthy men which uses moderate high IL2 doses as used in cancer treatment. Objective: The goal of this study was to quantify GH secretion after a single sc injection of IL2 in young and older healthy men in relation to dose, age and body composition. Design: This was a placebo-controlled, blinded, prospectively randomized cross-over study in 17 young subjects (mean age 24.1 yr) and 18 older subjects (mean age 63.9 yr). The subjects underwent 24 h of blood sampling at 10-min intervals, starting at 1800 h. At 2000 h IL2 (3 or 6 million units per m2 body surface) or saline was injected sc. Lights were off between 2300 and 0700 h. Outcome Measures: Deconvolution analysis of GH. Abdominal visceral fat (AVF) was calculated from single slice CT. Results: GH secretion (pulsatile and total) was negatively related to AVF (R=0.67, P<0.0001) and to age (R=0.56, P=0.001). These relations were maintained after IL2 administration. GH profiles were pulsatile under both experimental conditions. Since the effect of IL2 might be limited in time, GH deconvolution analyses were performed on the complete 24 h data series, the period with lights off and 6 h after IL2 administration. Total 24 h GH secretion decreased non-significantly from 74.6 ±10.2 to 67.5±7.4 µg/L (P=0.25) and pulsatile secretion from 69.4±9.8 to 62.2±7.4 µg/L (P=0.23). In the GLM procedure the effect of IL2 treatment was borderline significant (P=0.08), no interaction with age (P=0.28), but borderline with IL2 dose (P=0.07), and caused by decreased GH secretion (88 to 67 µg/L) at a low dose IL2. In a sub-analysis of the two age groups no effect on GH secretion in the older group was noted, in contrast to young subjects, especially on low dose IL2 (P=0.07). The analysis was refined further by calculating cumulative pulse masses in 2-h bins. By this approach it could be demonstrated that the cumulative GH pulse mass in older subjects across the 24 h was unchanged, while that in young subjects was temporarily inhibited in the bins between midnight and 0400 h (P=0.019 and 0.038). Conclusion: This study demonstrated that IL2 temporarily diminished GH secretion in young but not elderly volunteers. Pituitary hormone secretion by IL2 has not been studied as extensively as other cytokines, including IL1, IL6 and TNF. IL2 stimulates ACTH and TSH, inhibits LH and has no effect on GH secretion by rat pituitary (PNAS 58:185,1993). In patients with renal cancer IL2 infusion has no effect on GH levels (Anti-Cancer Res 10:753,1990. The present findings extend these observations to a large group of healthy volunteers, in whom we demonstrated previously suppression of the gonadal axis and activation of the HPA-axis (JCEM 101:539,2016, Endocr Connect 9:637,2010).