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.