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

Abstract

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.

Efficacy and safety of salbutamol in treatment of children with later-onset spinal muscular atrophy

“…分别于患儿治疗第1、3、6个月时随访复查血常规、血电解质、心电图等评估用药安全性。依据既往研究文献 ［ 10 - 12 ， 19 - 21 ］ 及沙丁胺醇常见不良反应，对药品成分过敏、心律失常、低血钾、骨骼肌震颤、躯体不适（恶心、呕吐、头晕）等进行评价。…”

“…SMA是一种常染色体隐性遗传神经肌肉疾病，因染色体5q12-13区 SMN1 基因缺失或突变导致SMN蛋白表达下降致病 ［ 1 ］ 。患者表现为四肢近端为主的进行性肌肉无力、萎缩，常伴多系统功能损害 ［ 1 - 3 ］ 。该病新生儿发病率约为1/10 000，中国人口 SMN1 突变携带率约1/42，居2岁以下婴幼儿致死致残性遗传病首位 ［ 1 ， 4 - 5 ］ 。人体内 SMN1 基因高度同源的 SMN2 基因可编码合成少量完整的全长SMN蛋白，帮助改善疾病表型 ［ 1 ， 6 ］ 。根据发病年龄及所能达到的最大运动里程，SMA可分为0（胎儿型）、Ⅰ（婴儿型）、Ⅱ和Ⅲ（晚发型）及Ⅳ型（成人型），其中Ⅰ~Ⅲ型在儿童期起病 ［ 1 ， 4 ， 6 ］ 。尽管SMA已进入疾病修正治疗时代，但国内疾病修正治疗药物的可及性不高 ［ 7 ］ 。沙丁胺醇作为一种选择性β 2 受体激动剂，除广泛应用于呼吸系统疾病外，近年来少数国外研究报道其可通过增强骨骼肌肌力来改善SMA患者肌无力症状 ［ 8 - 10 ］ 。本研究系沙丁胺醇治疗SMA前瞻性单臂Ⅲ期临床研究，通过对Ⅱ、Ⅲ型SMA患儿进行硫酸沙丁胺醇片口服治疗并随访6个月，探讨沙丁胺醇治疗SMA的临床疗效及安全性。…”

Estresse Oxidativo E Sinalizadores Inflamatórios Como Marcadores Do Quadro De Obesidade: Uma Breve Revisão Narrativa

“…Seu fluxo plasmático eleva de acordo com o volume do exercício e a massa muscular, podendo subir centenas de vezes, quando comparado com os níveis repouso (VANDERVEEN et al, 2019). Além do mais, essa citocina, após o exercício crônico, não teve redução, ao contrário, continuou com seus níveis plasmáticos elevados (HOSTRUP et al, 2022). Pesquisas citam que, o exercício crônico de intensidade reduzida pode inibir as citocinas pró-inflamatórias, como TNF-α, leptina e MCP-1 (DA ROCHA et al, 2021).…”

Secretion of Interleukin 6 in Human Skeletal Muscle Cultures Depends on Ca2+ Signalling

“…Other cellular stimuli could also induce IL-6 release. Adrenergic receptors can induce secretion in rodent muscles [19,20] and cultures [20] and also in humans during exercise [21]. Nitric oxide [22] and hyperthermia [23] can also release IL-6 in rodent models.…”