Dose effects of recombinant human interleukin-6 on pituitary hormone secretion and energy expenditure.
Level 4 - case-series / case-control
Small, non-randomized, uncontrolled dose-escalation experimental study in healthy volunteers
PubMed 9258919 · doi:10.1159/000127219
What was done
Fifteen healthy male volunteers received a single subcutaneous injection of recombinant human interleukin-6 (IL-6) across five escalating dose tiers (0.1, 0.3, 1.0, 3.0, and 10.0 mcg/kg body weight; n=3 per dose). Researchers measured resting metabolic rate (RMR) via indirect calorimetry and sampled plasma anterior pituitary hormones and vasopressin half-hourly from baseline through 4 hours post-injection.
What was found
IL-6 was well tolerated without significant adverse effects. Doses of 3.0 and 10.0 mcg/kg induced dose-dependent RMR increases beginning at 60 minutes and peaking between 180 and 240 minutes. ACTH increased dose-dependently at 3.0 and 10.0 mcg/kg, peaking at 150 pg/ml and 255 pg/ml at 60 minutes before returning to baseline by 4 hours; cortisol peaked between 90 and 150 minutes and remained elevated at 4 hours. Growth hormone showed a bell-shaped response peaking at 3.0 mcg/kg (approximately 100-fold stimulation). Prolactin showed a similar bell-shaped increase, TSH decreased progressively over 240 minutes, and gonadotropins showed no clear changes.
Why it matters
This study demonstrates in humans that systemic IL-6 can simultaneously activate the hypothalamic-pituitary-adrenal axis, alter other pituitary hormones, and elevate energy expenditure, supporting a role for IL-6 in immune-endocrine-metabolic cross-talk.
Limits
The sample size was very small (n=3 per dose group, total n=15) and included only healthy men. The study lacked a placebo or vehicle control group, and follow-up was limited to 4 hours post-injection.
Cited by
- supports Interleukin-6 (IL-6) can directly re-trigger the hypothalamic-pituitary-adrenal (HPA) axis without the presence of an external stressor.