IL-18 Binding Protein, a biomarker of strength maintenance after surgery but reduced physical performance in age-related sarcopenia

TL;DR

This study explores how IL-18 Binding Protein (IL-18BP) affects muscle strength after surgery and in age-related muscle loss.

Contribution

The study identifies IL-18BP as a biomarker for strength maintenance after surgery and reduced physical performance in sarcopenia.

Findings

IL-18BP is associated with strength maintenance after surgery.

Higher IL-18BP levels correlate with reduced muscle strength in men with sarcopenia.

IL-18BP is linked to mitochondrial gene activity in muscle.

Abstract

Inflammation is thought to contribute to muscle loss in acute and chronic sarcopenia. Which inflammatory proteins contribute to sarcopenia in any condition is not clear. In a well-characterised cohort of patients experiencing acute sarcopenia following surgery, we used a proteomic screen of plasma to identify proteins associated with the change in strength. We compared change in handgrip strength over 7 days in surgery patients with plasma protein levels quantified by SOMAscan before and 24h after surgery. Surgery increased circulating concentrations of 295 proteins and decreased 301. Analysis of the day 1 protein levels showed that IL-18BP associated with maintenance of strength. To further investigate relationships between IL18BP and strength, IL-18BP as well as its ligands IL-18 and IL-37, were quantified by ELISA and in surgery patients and in 129 individuals (68 women) with age-related sarcopenia recruited to the Leucine and/or ACE inhibitor (LACE) trial. In LACE participants, the proteins were compared to grip strength, quadriceps maximal voluntary contraction (QMVC) and 6-minute walk distance (6MWD) and baseline SARC-F score. In the LACE cohort, IL-18BP was negatively associated with grip strength in men but not women, at baseline (r = −0.314, p = 0.014) and 12 months (r = −0.446, p = 0.001). QMVC and 6MWD showed similar associations. IL-18BP was associated with SARC-F in men (r = 0.389, p = 0.003) but not women. Investigation of SOMAscan data from surgery patients at baseline showed similar inverse associations of IL-18BP with strength. Comparison of circulating IL-18BP with the muscle transcriptome in these patients showed negative enrichment for mitochondrial genes. Analysis of the ligands showed that free IL-18 was proportional to 6MWD. After surgery high IL-18BP levels associate with maintenance of strength but circulating IL-18BP concentrations are associated with reduced muscle strength in men with sarcopenia. These data are consistent with known effects of IL-18BP ligands on the maintenance of mitochondrial function.

Figures