Skeletal Muscle Myokine Expression in Critical Illness, Association With Outcome and Impact of Therapeutic Interventions.

Context: Muscle expresses and secretes several myokines that bring about benefits in distant organs.

Objective: We investigated the impact of critical illness on muscular expression of irisin, kynurenine aminotransferases, and amylase; association with clinical outcome; and impact of interventions that attenuate muscle wasting/weakness.

Methods: We studied critically ill patients who participated in 2 randomized controlled trials (EPaNIC/NESCI) and documented time profiles in critically ill mice. Included in the study were 174 intensive care unit (ICU) patients (day 8 ± 1) vs 19 matched controls, and 60 mice subjected to surgery/sepsis vs 60 pair-fed healthy mice. Interventions studied included 7-day neuromuscular electrical stimulation (NMES), and withholding parenteral nutrition (PN) in the first ICU week (late PN) vs early PN. The main outcome measures were (irisin- precursor), , and amylase mRNA expression in skeletal muscle.

Results: Critically ill patients showed 34% to 80% lower mRNA expression of , , and amylases than controls ( < .0001). Critically ill mice showed time-dependent reductions in all mRNAs compared with healthy mice ( ≤ .04). The lower expression in patients was independently associated with a higher ICU mortality ( = .015) and ICU-acquired weakness ( = .012), whereas the lower amylase expression in ICU survivors was independently associated with a longer ICU stay ( = .0060). Lower amylase expression was independently associated with a lower risk of death ( = .048), and lower expression with a lower risk of weakness ( = .022). NMES increased expression compared with unstimulated muscle ( = .016), and late PN patients had a higher expression than early PN patients ( = .022).

Conclusion: Expression of the studied myokines was affected by critical illness and associated with clinical outcomes, with limited effects of interventions that attenuate muscle wasting or weakness.