Beta₂-agonist increases skeletal muscle interleukin 6 production and release in response to resistance exercise in men

Objective: Several tissues produce and release interleukin-6 (IL-6) in response to beta₂-adrenergic stimulation with selective agonists (beta₂-agonists). Moreover, exercise stimulates muscle IL-6 production, but whether beta₂-agonists regulate skeletal muscle production and release of IL-6 in humans, in association with exercise remains to be clarified. Thus, we investigated leg IL-6 release in response to beta₂-agonist salbutamol in lean young men at rest and in recovery from resistance exercise.

Design: The study employed a randomized controlled crossover design, where 12 men ingested either salbutamol (16 mg) or placebo for 4 days, followed by the last dose (24 mg) administered 1½ h before exercise. Arterial and femoral venous plasma IL-6 as well as femoral artery blood flow was measured before and ½-5 h in recovery from quadriceps muscle resistance exercise. Furthermore, vastus lateralis muscle biopsies were collected ½ and 5 h after exercise for determination of mRNA levels of IL-6 and Tumor Necrosis Factor (TNF)-α.

Results: Average leg IL-6 release was 1.7-fold higher (p=0.01) for salbutamol than placebo, being 138±76 and 79±66 pg∙min^-1 (mean±SD) for salbutamol and placebo, respectively, but IL-6 release was not significantly different between treatments within specific sampling points at rest and after exercise. Muscle IL-6 mRNA was 1.5 and 1.7-fold higher (p=0.001) for salbutamol than placebo ½ and 5 h after exercise, respectively, whereas no significant treatment differences were observed for TNF-α mRNA.

Conclusions: Beta₂-adrenergic stimulation with high doses of the selective beta₂-agonist salbutamol, preceeded by 4 consecutive daily doses, induces transcription of IL-6 in skeletal muscle in response to resistance exercise and increases muscle IL-6 release in lean individuals.