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

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.