The translational initiation factors are central components of the protein translation machinery and EIF4 is the proposed rate limiting factor for protein translational. While the partners of EIF4E, EIF4A1, EIF4G1 and EIF3S10 were all up-regulated in the ICU patients, EIF4E is unchanged at the mRNA level. In combination with the increased expression of the tRNA synthetases, MARS, LARS and RARS it would appear that a substantial yet incomplete attempt was made to promote muscle protein synthesis, similar to that observed for the mitochondria. This appears to have failed perhaps reflecting a lack of up-regulation of EIF4E, however, EIF4E is not considered to be regulated to a great extent, at the mRNA level, and thus further analysis is merited. Overall, it is clear that the lack of gross changes in in vivo protein dynamics must obscure critical alterations in specific protein formation, such that combing protein measurements with global transcriptomics provides a powerful solution to understanding the nature of tissue remodelling in multiple organ failure patients. When looking for novel regulators of altered protein production from mRNA, microRNA��s as global regulators of protein synthesis are of great interest. In the ICU patients, we found a compelling 500% increase in the precursor for mir-21. When we measured the mature form of mir-21, we observed no significant change in mir-21 levels in skeletal muscle of ICU patients when compared with controls. This is important as it has been recently identified that reduction in PTEN expression could be a compensatory mechanism to prevent muscle protein degradation and mir-21 is a validated target of PTEN. Mature mir-21 is processed from a 3,433 long nucleotide pri-mir-21. Thus, despite the substantial increase in the mir-21 precursor, only modest changes in mature miRNA occurred. Interestingly, IL-6 is 3,4,5-Trimethoxyphenylacetic acid activated in ICU patients and has been reported to increase mir-21 in tumour cell lines mediated via STAT3. The IL-6 receptor increases in skeletal muscle in response to both acute and chronic stimuli, suggesting an increased responsiveness to IL-6. We detected a 10-fold increase in the IL-6 receptor in skeletal muscle of ICU patients, when compared with Tulathromycin B healthy controls, along with a 1.8-fold increase in STAT-3, the intracellular mediator of IL-6 signalling.